Children's Drawings of Physical Activity: Implications for Needs Assessment and Programming

ERIC Educational Resources Information Center

Sharpe, Patricia A.; Greaney, Mary L.; Royce, Sherer W.; Fields, Regina M.

2004-01-01

This article shows how to explore children's perceptions of physical activity through content analysis of their artwork. Ninety-one children drew pictures of what they perceived to be "physical activity" and created a slogan for promoting physical activity in their community. Drawing content revealed types of popular activities,…

Specific cerebellar activation during Braille reading in blind subjects.

PubMed

Gizewski, Elke R; Timmann, Dagmar; Forsting, Michael

2004-07-01

The traditional view that the cerebellum is involved only in the control of movements has been changed recently. It has been suggested that the human cerebellum is involved in cognition and language. Likewise, besides cortical activity in sensorimotor and visual areas, an increased global activation of the cerebellum has been revealed during Braille reading in blind subjects. Our purpose was to investigate whether there is cerebellar activation during Braille reading by blind subjects other than sensorimotor activation related to finger movements. Early blind and normal sighted subjects were studied with functional magnetic resonance imaging (fMRI) during Braille reading, tactile discrimination of nonsense dots, dots forming symbols, and finger tapping. The experiments were done in block design. Echo planar imaging sequences were carried out on a 1.5-T MR scanner. All blind individuals reading Braille showed robust activation of the posterior and lateral aspects of cerebellar hemispheral lobules Crus I bilaterally but more predominately on the right side. Additionally, activation was present in the medial cerebellum within lobules IV, V, and VIIIA, predominantly on the right. Discriminating nonsense dots did not reveal any activation of Crus I, but did reveal activation within the medial part of lobules IV, V, and VIIIA, predominately on the right. Analysis of sighted subjects during reading of printed text revealed activation of the posterolateral cerebellar hemisphere in Crus I bilaterally, predominantly on the right. Tactile analysis of dots representing symbols revealed an activation in lobules IV and VIII and in right Crus II but not in Crus I. In conclusion, parts of cerebellar activation during Braille reading in blind subjects (i.e., within lobules IV, V, and VIII) overlap with the known hand representation within the cerebellum and are likely related to the sensorimotor part of the task. Cerebellar activation during Braille reading within bilateral Crus I may be due to language processes or inner speech similar to those found during text reading in normal sighted subjects. Object recognition did not account for Crus I activation. Copyright 2004 Wiley-Liss, Inc.

Augmenting the activity of antifungal agents against aspergilli using structural analogues of benzoic acid as chemosensitizing agents

USDA-ARS?s Scientific Manuscript database

Several benzoic acid analogs showed antifungal activity against strains of Aspergillus flavus, A. fumigatus and A. terreus, causative agents of human aspergillosis. Structure-activity analysis revealed that antifungal activities of benzoic and gallic acids increased by addition of a methyl, methoxyl...

The cholesterol-dependent cytolysins pneumolysin and streptolysin O require binding to red blood cell glycans for hemolytic activity

PubMed Central

Shewell, Lucy K.; Harvey, Richard M.; Higgins, Melanie A.; Day, Christopher J.; Hartley-Tassell, Lauren E.; Chen, Austen Y.; Gillen, Christine M.; James, David B. A.; Alonzo, Francis; Torres, Victor J.; Walker, Mark J.; Paton, Adrienne W.; Paton, James C.; Jennings, Michael P.

2014-01-01

The cholesterol-dependent cytolysin (CDC) pneumolysin (Ply) is a key virulence factor of Streptococcus pneumoniae. Membrane cholesterol is required for the cytolytic activity of this toxin, but it is not clear whether cholesterol is the only cellular receptor. Analysis of Ply binding to a glycan microarray revealed that Ply has lectin activity and binds glycans, including the Lewis histo-blood group antigens. Surface plasmon resonance analysis showed that Ply has the highest affinity for the sialyl LewisX (sLeX) structure, with a Kd of 1.88 × 10−5 M. Ply hemolytic activity against human RBCs showed dose-dependent inhibition by sLeX. Flow cytometric analysis and Western blots showed that blocking binding of Ply to the sLeX glycolipid on RBCs prevents deposition of the toxin in the membrane. The lectin domain responsible for sLeX binding is in domain 4 of Ply, which contains candidate carbohydrate-binding sites. Mutagenesis of these predicted carbohydrate-binding residues of Ply resulted in a decrease in hemolytic activity and a reduced affinity for sLeX. This study reveals that this archetypal CDC requires interaction with the sLeX glycolipid cellular receptor as an essential step before membrane insertion. A similar analysis conducted on streptolysin O from Streptococcus pyogenes revealed that this CDC also has glycan-binding properties and that hemolytic activity against RBCs can be blocked with the glycan lacto-N-neotetraose by inhibiting binding to the cell surface. Together, these data support the emerging paradigm shift that pore-forming toxins, including CDCs, have cellular receptors other than cholesterol that define target cell tropism. PMID:25422425

The cholesterol-dependent cytolysins pneumolysin and streptolysin O require binding to red blood cell glycans for hemolytic activity.

PubMed

Shewell, Lucy K; Harvey, Richard M; Higgins, Melanie A; Day, Christopher J; Hartley-Tassell, Lauren E; Chen, Austen Y; Gillen, Christine M; James, David B A; Alonzo, Francis; Torres, Victor J; Walker, Mark J; Paton, Adrienne W; Paton, James C; Jennings, Michael P

2014-12-09

The cholesterol-dependent cytolysin (CDC) pneumolysin (Ply) is a key virulence factor of Streptococcus pneumoniae. Membrane cholesterol is required for the cytolytic activity of this toxin, but it is not clear whether cholesterol is the only cellular receptor. Analysis of Ply binding to a glycan microarray revealed that Ply has lectin activity and binds glycans, including the Lewis histo-blood group antigens. Surface plasmon resonance analysis showed that Ply has the highest affinity for the sialyl LewisX (sLeX) structure, with a K(d) of 1.88 × 10(-5) M. Ply hemolytic activity against human RBCs showed dose-dependent inhibition by sLeX. Flow cytometric analysis and Western blots showed that blocking binding of Ply to the sLeX glycolipid on RBCs prevents deposition of the toxin in the membrane. The lectin domain responsible for sLeX binding is in domain 4 of Ply, which contains candidate carbohydrate-binding sites. Mutagenesis of these predicted carbohydrate-binding residues of Ply resulted in a decrease in hemolytic activity and a reduced affinity for sLeX. This study reveals that this archetypal CDC requires interaction with the sLeX glycolipid cellular receptor as an essential step before membrane insertion. A similar analysis conducted on streptolysin O from Streptococcus pyogenes revealed that this CDC also has glycan-binding properties and that hemolytic activity against RBCs can be blocked with the glycan lacto-N-neotetraose by inhibiting binding to the cell surface. Together, these data support the emerging paradigm shift that pore-forming toxins, including CDCs, have cellular receptors other than cholesterol that define target cell tropism.

Fragments of Bacterial Endoglycosidase S and Immunoglobulin G Reveal Subdomains of Each That Contribute to Deglycosylation*

PubMed Central

Dixon, Emma V.; Claridge, Jolyon K.; Harvey, David J.; Baruah, Kavitha; Yu, Xiaojie; Vesiljevic, Snezana; Mattick, Susan; Pritchard, Laura K.; Krishna, Benjamin; Scanlan, Christopher N.; Schnell, Jason R.; Higgins, Matthew K.; Zitzmann, Nicole; Crispin, Max

2014-01-01

Endoglycosidase S (EndoS) is a glycoside-hydrolase secreted by the bacterium Streptococcus pyogenes. EndoS preferentially hydrolyzes the N-linked glycans from the Fc region of IgG during infection. This hydrolysis impedes Fc functionality and contributes to the immune evasion strategy of S. pyogenes. Here, we investigate the mechanism of human serum IgG deactivation by EndoS. We expressed fragments of IgG1 and demonstrated that EndoS was catalytically active against all of them including the isolated CH2 domain of the Fc domain. Similarly, we sought to investigate which domains within EndoS could contribute to activity. Bioinformatics analysis of the domain organization of EndoS confirmed the previous predictions of a chitinase domain and leucine-rich repeat but also revealed a putative carbohydrate binding module (CBM) followed by a C-terminal region. Using expressed fragments of EndoS, circular dichroism of the isolated CBM, and a CBM-C-terminal region fusion revealed folded domains dominated by β sheet and α helical structure, respectively. Nuclear magnetic resonance analysis of the CBM with monosaccharides was suggestive of carbohydrate binding functionality. Functional analysis of truncations of EndoS revealed that, whereas the C-terminal of EndoS is dispensable for activity, its deletion impedes the hydrolysis of IgG glycans. PMID:24668806

Functional characterization of the turkey macrophage migration inhibitory factor.

PubMed

Park, Myeongseon; Kim, Sungwon; Fetterer, Raymond H; Dalloul, Rami A

2016-08-01

Macrophage migration inhibitory factor (MIF) is a soluble protein that inhibits the random migration of macrophages and plays a pivotal immunoregulatory function in innate and adaptive immunity. The aim of this study was to clone the turkey MIF (TkMIF) gene, express the active protein, and characterize its basic function. The full-length TkMIF gene was amplified from total RNA extracted from turkey spleen, followed by cloning into a prokaryotic (pET11a) expression vector. Sequence analysis revealed that TkMIF consists of 115 amino acids with 12.5 kDa molecular weight. Multiple sequence alignment revealed 100%, 65%, 95% and 92% identity with chicken, duck, eagle and zebra finch MIFs, respectively. Recombinant TkMIF (rTkMIF) was expressed in Escherichia coli and purified through HPLC and endotoxin removal. SDS-PAGE analysis revealed an approximately 13.5 kDa of rTkMIF monomer containing T7 tag in soluble form. Western blot analysis showed that anti-chicken MIF (ChMIF) polyclonal antisera detected a monomer form of TkMIF at approximately 13.5 kDa size. Further functional analysis revealed that rTkMIF inhibits migration of both mononuclear cells and splenocytes in a dose-dependent manner, but was abolished by the addition of anti-ChMIF polyclonal antisera. qRT-PCR analysis revealed elevated transcripts of pro-inflammatory cytokines by rTkMIF in LPS-stimulated monocytes. rTkMIF also led to increased levels of IFN-γ and IL-17F transcripts in Con A-activated splenocytes, while IL-10 and IL-13 transcripts were decreased. Overall, the sequences of both the turkey and chicken MIF have high similarity and comparable biological functions with respect to migration inhibitory activities of macrophages and enhancement of pro-inflammatory cytokine expression, suggesting that turkey and chicken MIFs would be biologically cross-reactive. Copyright © 2016 Elsevier Ltd. All rights reserved.

Active medulloblastoma enhancers reveal subgroup-specific cellular origins

PubMed Central

Lin, Charles Y.; Erkek, Serap; Tong, Yiai; Yin, Linlin; Federation, Alexander J.; Zapatka, Marc; Haldipur, Parthiv; Kawauchi, Daisuke; Risch, Thomas; Warnatz, Hans-Jörg; Worst, Barbara C.; Ju, Bensheng; Orr, Brent A.; Zeid, Rhamy; Polaski, Donald R.; Segura-Wang, Maia; Waszak, Sebastian M.; Jones, David T.W.; Kool, Marcel; Hovestadt, Volker; Buchhalter, Ivo; Sieber, Laura; Johann, Pascal; Chavez, Lukas; Gröschel, Stefan; Ryzhova, Marina; Korshunov, Andrey; Chen, Wenbiao; Chizhikov, Victor V.; Millen, Kathleen J.; Amstislavskiy, Vyacheslav; Lehrach, Hans; Yaspo, Marie-Laure; Eils, Roland; Lichter, Peter; Korbel, Jan O.; Pfister, Stefan M.; Bradner, James E.; Northcott, Paul A.

2016-01-01

Summary Medulloblastoma is a highly malignant paediatric brain tumour, often inflicting devastating consequences on the developing child. Genomic studies have revealed four distinct molecular subgroups with divergent biology and clinical behaviour. An understanding of the regulatory circuitry governing the transcriptional landscapes of medulloblastoma subgroups, and how this relates to their respective developmental origins, is lacking. Using H3K27ac and BRD4 ChIP-Seq, coupled with tissue-matched DNA methylation and transcriptome data, we describe the active cis-regulatory landscape across 28 primary medulloblastoma specimens. Analysis of differentially regulated enhancers and super-enhancers reinforced inter-subgroup heterogeneity and revealed novel, clinically relevant insights into medulloblastoma biology. Computational reconstruction of core regulatory circuitry identified a master set of transcription factors, validated by ChIP-Seq, that are responsible for subgroup divergence and implicate candidate cells-of-origin for Group 4. Our integrated analysis of enhancer elements in a large series of primary tumour samples reveals insights into cis-regulatory architecture, unrecognized dependencies, and cellular origins. PMID:26814967

How Active Are Teens during Their Out-of-School Time? The View from Chicago. Chapin Hall Issue Brief

ERIC Educational Resources Information Center

Goerge, Robert M.; Cusick, Gretchen Ruth; Guiltinan, Shannon

2009-01-01

This issue brief explores levels of physical activity among high school students in Chicago Public Schools, including participation in sports, informal exercise, and other activities. Latent class analysis was used to classify students' levels of physical activity, revealing low levels of activity among most high school students. Multilevel…

DOE Office of Scientific and Technical Information (OSTI.GOV)

Unterberger, Claudia; Hanson, Steven; Department of Infection, Immunity and Inflammation, University of Leicester, University Road, Leicester LE1 9HN

Little is known about determinants regulating expression of Mannan-binding lectin associated serine protease-2 (MASP-2), the effector component of the lectin pathway of complement activation. Comparative bioinformatic analysis of the MASP2 promoter regions in human, mouse, and rat, revealed conservation of two putative Stat binding sites, termed StatA and StatB. Site directed mutagenesis specific for these sites was performed. Transcription activity was decreased 5-fold when StatB site was mutated in the wildtype reporter gene construct. Gel retardation and competition assays demonstrated that proteins contained in the nuclear extract prepared from HepG2 specifically bound double-stranded StatB oligonucleotides. Supershift analysis revealed Stat3 tomore » be the major specific binding protein. We conclude that Stat3 binding is important for MASP2 promoter activity.« less

Are numbers grounded in a general magnitude processing system? A functional neuroimaging meta-analysis.

PubMed

Sokolowski, H Moriah; Fias, Wim; Bosah Ononye, Chuka; Ansari, Daniel

2017-10-01

It is currently debated whether numbers are processed using a number-specific system or a general magnitude processing system, also used for non-numerical magnitudes such as physical size, duration, or luminance. Activation likelihood estimation (ALE) was used to conduct the first quantitative meta-analysis of 93 empirical neuroimaging papers examining neural activation during numerical and non-numerical magnitude processing. Foci were compiled to generate probabilistic maps of activation for non-numerical magnitudes (e.g. physical size), symbolic numerical magnitudes (e.g. Arabic digits), and nonsymbolic numerical magnitudes (e.g. dot arrays). Conjunction analyses revealed overlapping activation for symbolic, nonsymbolic and non-numerical magnitudes in frontal and parietal lobes. Contrast analyses revealed specific activation in the left superior parietal lobule for symbolic numerical magnitudes. In contrast, small regions in the bilateral precuneus were specifically activated for nonsymbolic numerical magnitudes. No regions in the parietal lobes were activated for non-numerical magnitudes that were not also activated for numerical magnitudes. Therefore, numbers are processed using both a generalized magnitude system and format specific number regions. Copyright © 2017 Elsevier Ltd. All rights reserved.

Causality analysis of leading singular value decomposition modes identifies rotor as the dominant driving normal mode in fibrillation

NASA Astrophysics Data System (ADS)

Biton, Yaacov; Rabinovitch, Avinoam; Braunstein, Doron; Aviram, Ira; Campbell, Katherine; Mironov, Sergey; Herron, Todd; Jalife, José; Berenfeld, Omer

2018-01-01

Cardiac fibrillation is a major clinical and societal burden. Rotors may drive fibrillation in many cases, but their role and patterns are often masked by complex propagation. We used Singular Value Decomposition (SVD), which ranks patterns of activation hierarchically, together with Wiener-Granger causality analysis (WGCA), which analyses direction of information among observations, to investigate the role of rotors in cardiac fibrillation. We hypothesized that combining SVD analysis with WGCA should reveal whether rotor activity is the dominant driving force of fibrillation even in cases of high complexity. Optical mapping experiments were conducted in neonatal rat cardiomyocyte monolayers (diameter, 35 mm), which were genetically modified to overexpress the delayed rectifier K+ channel IKr only in one half of the monolayer. Such monolayers have been shown previously to sustain fast rotors confined to the IKr overexpressing half and driving fibrillatory-like activity in the other half. SVD analysis of the optical mapping movies revealed a hierarchical pattern in which the primary modes corresponded to rotor activity in the IKr overexpressing region and the secondary modes corresponded to fibrillatory activity elsewhere. We then applied WGCA to evaluate the directionality of influence between modes in the entire monolayer using clear and noisy movies of activity. We demonstrated that the rotor modes influence the secondary fibrillatory modes, but influence was detected also in the opposite direction. To more specifically delineate the role of the rotor in fibrillation, we decomposed separately the respective SVD modes of the rotor and fibrillatory domains. In this case, WGCA yielded more information from the rotor to the fibrillatory domains than in the opposite direction. In conclusion, SVD analysis reveals that rotors can be the dominant modes of an experimental model of fibrillation. Wiener-Granger causality on modes of the rotor domains confirms their preferential driving influence on fibrillatory modes.

Mining the Social Mediome

PubMed Central

Asch, David A.; Rader, Daniel J.; Merchant, Raina

2015-01-01

The experiences and behaviors revealed in our everyday lives provide as much insight into health and disease as any analysis of our genome could ever produce. These characteristics are not found in the genome, but may be revealed in our online activities which make up our social mediome. PMID:26341614

Abnormal Brain Activation During Theory of Mind Tasks in Schizophrenia: A Meta-Analysis.

PubMed

Kronbichler, Lisa; Tschernegg, Melanie; Martin, Anna Isabel; Schurz, Matthias; Kronbichler, Martin

2017-10-21

Social cognition abilities are severely impaired in schizophrenia (SZ). The current meta-analysis used foci of 21 individual studies on functional abnormalities in the schizophrenic brain in order to identify regions that reveal convergent under- or over-activation during theory of mind (TOM) tasks. Studies were included in the analyses when contrasting tasks that require the processing of mental states with tasks which did not. Only studies that investigated patients with an ICD or DSM diagnosis were included. Quantitative voxel-based meta-analyses were done using Seed-based d Mapping software. Common TOM regions like medial-prefrontal cortex and temporo-parietal junction revealed abnormal activation in schizophrenic patients: Under-activation was identified in the medial prefrontal cortex, left orbito-frontal cortex, and in a small section of the left posterior temporo-parietal junction. Remarkably, robust over-activation was identified in a more dorsal, bilateral section of the temporo-parietal junction. Further abnormal activation was identified in medial occipito-parietal cortex, right premotor areas, left cingulate gyrus, and lingual gyrus. The findings of this study suggest that SZ patients simultaneously show over- and under-activation in TOM-related regions. Especially interesting, temporo-parietal junction reveals diverging activation patterns with an under-activating left posterior and an over-activating bilateral dorsal section. In conclusion, SZ patients show less specialized brain activation in regions linked to TOM and increased activation in attention-related networks suggesting compensatory effects. © The Author 2017. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center.

Research regarding biodegradable properties of food polymeric products under microorganism activity

NASA Astrophysics Data System (ADS)

Opran, Constantin; Lazar, Veronica; Fierascu, Radu Claudiu; Ditu, Lia Mara

2018-02-01

Aim of this research is the structural analysis by comparison of the biodegradable properties of two polymeric products made by non-biodegradable polymeric material (polypropylene TIPPLEN H949 A) and biodegradable polymeric material (ECOVIO IS 1335), under microorganism activity in order to give the best solution for the manufacture of food packaging biodegradable products. It presents the results of experimental determinations on comparative analysis of tensile strength for the two types of polymers. The sample weight variations after fungal biodegradation activity revealed that, after 3 months, there are no significant changes in polymeric substratum for non-biodegradable polymeric. The microscopically analysis showed that the fungal filaments did not strongly adhered on the non-biodegradable polymeric material, instead, both filamentous fungi strains adhered and covered the surface of the biodegradable sample with germinated filamentous conidia. The spectral analysis of polymer composition revealed that non-biodegradable polymer polypropylene spectra are identical for control and for samples that were exposed to fungal activity, suggesting that this type of sample was not degraded by the fungi strains. Instead, for biodegradable polymer sample, it was observed significant structural changes across multiple absorption bands, suggesting enzyme activity manifested mainly by Aspergillus niger strain. Structural analysis of interdisciplinary research results, lead, to achieving optimal injection molded technology emphasizing technological parameters, in order to obtain food packaging biodegradable products.

The Potential for Development of Russian Youth Social Activity

ERIC Educational Resources Information Center

Savotina, Nataliya

2016-01-01

The article deals with scientific and applied topicality of studying the problem of children and youth social activity. Spheres of social activity display in European tradition, in particular, the European Charter, Great Britain, have been revealed. Comparative analysis of understanding the essence of such a phenomenon in Western theories and…

Peptidome analysis of amniotic fluid from pregnancies with preeclampsia.

PubMed

Qian, Yating; Zhang, Lei; Rui, Can; Ding, Hongjuan; Mao, Pengyuan; Ruan, Hongjie; Jia, Ruizhe

2017-11-01

Preeclampsia (PE), a life‑threatening, complicated pregnancy‑associated disease, has recently become a research focus in obstetrics. However, the peptidome of the amniotic fluid in PE patients has rarely been investigated. The present study used peptidomic profiling to perform a comparative analysis of human amniotic fluid between normal and PE pregnancies. Centrifugal ultrafiltration and liquid chromatography‑tandem mass spectrometry (LC‑MS/MS) was combined with isotopomeric dimethyl labels to gain a deeper understanding of the role of proteins and the peptidome in the onset of PE. Following ultrafiltration and LC‑MS/MS, 352 peptides were identified. Of these, 23 peptides were observed to be significantly differentially expressed (6 downregulated and 17 upregulated; P<0.05). Using Gene Ontology and Blastp analyses, the functions and biological activities of these 23 peptides were identified and revealed to include autophagy, signal transduction, receptor activity, enzymatic activity and nucleic acid binding. In addition, a bibliographic search revealed that some of the identified peptides, including Titin, are crucial to the pathogenesis underlying PE. The present study identified 23 peptides expressed at significantly different levels in the amniotic fluid of PE and normal pregnancies. A comprehensive peptidome analysis is more efficient than a simple biomarker analysis at revealing deficiencies and improving the detection rate in diseases. These analyses therefore provide a substantial advantage in applications aimed at the discovery of disease‑specific biomarkers.

Pedagogical Beliefs, Activity Choice and Structure, and Adult-Child Interaction in Nursery Classrooms

ERIC Educational Resources Information Center

Blay, Josepha A.; Ireson, Judith

2009-01-01

A qualitative analysis of four cooking activities undertaken in two nursery classes reveals relationships between the adults' pedagogical beliefs, the choice and structuring of activities, and the nature of adult-child participation. Four adults each planned and carried out separately, one cooking activity of their choice with a small group of…

Lipid reducing activity and toxicity profiles of a library of polyphenol derivatives.

PubMed

Urbatzka, Ralph; Freitas, Sara; Palmeira, Andreia; Almeida, Tiago; Moreira, João; Azevedo, Carlos; Afonso, Carlos; Correia-da-Silva, Marta; Sousa, Emilia; Pinto, Madalena; Vasconcelos, Vitor

2018-05-10

Obesity is an increasing epidemic worldwide and novel treatments are urgently needed. Polyphenols are natural compounds derived from plants, which are known in particular for their antioxidant properties. However, some polyphenols were described to possess anti-obesity activities in vitro and in vivo. In this study, we aimed to screen a library of 85 polyphenol derivatives for their lipid reducing activity and toxicity. Compounds were analyzed at 5 μM with the zebrafish Nile red fluorescence fat metabolism assay and for general toxicity in vivo. To improve the safety profile, compounds were screened at 50 μM in murine preadipocytes in vitro for cytotoxicity. Obtained activity data were used to create a 2D-QSAR (quantitative structure activity relationship) model. 38 polyphenols showed strong lipid reducing activity. Toxicity analysis revealed that 18 of them did not show any toxicity in vitro or in vivo. QSAR analysis revealed the importance of the number of rings, fractional partial positively charged surface area, relative positive charge, relative number of oxygen atoms, and partial negative surface area for lipid-reducing activity. The five most potent compounds with EC 50 values in the nanomolar range for lipid reducing activity and without any toxic effects are strong candidates for future research and development into anti-obesity drugs. Molecular profiling for fasn, sirt1, mtp and ppary revealed one compound that reduced significantly fasn mRNA expression. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Characterization of bafilomycin biosynthesis in Kitasatospora setae KM-6054 and comparative analysis of gene clusters in Actinomycetales microorganisms.

PubMed

Nara, Ayako; Hashimoto, Takuya; Komatsu, Mamoru; Nishiyama, Makoto; Kuzuyama, Tomohisa; Ikeda, Haruo

2017-05-01

Bafilomycins A 1 , C 1 and B 1 (setamycin) produced by Kitasatospora setae KM-6054 belong to the plecomacrolide family, which exhibit antibacterial, antifungal, antineoplastic and immunosuppressive activities. An analysis of gene clusters from K. setae KM-6054 governing the biosynthesis of bafilomycins revealed that it contains five large open reading frames (ORFs) encoding the multifunctional polypeptides of bafilomycin polyketide synthases (PKSs). These clustered PKS genes, which are responsible for bafilomycin biosynthesis, together encode 11 homologous sets of enzyme activities, each catalyzing a specific round of polyketide chain elongation. The region contains an additional 13 ORFs spanning a distance of 73 287 bp, some of which encode polypeptides governing other key steps in bafilomycin biosynthesis. Five ORFs, BfmB, BfmC, BfmD, BfmE and BfmF, were involved in the formation of methoxymalonyl-acyl carrier protein (ACP). Two possible regulatory genes, bfmR and bfmH, were found downstream of the above genes. A gene-knockout analysis revealed that BfmR was only a transcriptional regulator for the transcription of bafilomycin biosynthetic genes. Two genes, bfmI and bfmJ, were found downstream of bfmH. An analysis of these gene-disruption mutants in addition to an enzymatic analysis of BfmI and BfmJ revealed that BfmJ activated fumarate and BfmI functioned as a catalyst to form a fumaryl ester at the C21 hydroxyl residue of bafilomycin A 1 . A comparative analysis of bafilomycin gene clusters in K. setae KM-6054, Streptomyces lohii JCM 14114 and Streptomyces griseus DSM 2608 revealed that each ORF of both gene clusters in two Streptomyces strains were quite similar to each other. However, each ORF of gene cluster in K. setae KM-6054 was of lower similarity to that of corresponding ORF in the two Streptomyces species.

Time-Varying Networks of Inter-Ictal Discharging Reveal Epileptogenic Zone.

PubMed

Zhang, Luyan; Liang, Yi; Li, Fali; Sun, Hongbin; Peng, Wenjing; Du, Peishan; Si, Yajing; Song, Limeng; Yu, Liang; Xu, Peng

2017-01-01

The neuronal synchronous discharging may cause an epileptic seizure. Currently, most of the studies conducted to investigate the mechanism of epilepsy are based on EEGs or functional magnetic resonance imaging (fMRI) recorded during the ictal discharging or the resting-state, and few studies have probed into the dynamic patterns during the inter-ictal discharging that are much easier to record in clinical applications. Here, we propose a time-varying network analysis based on adaptive directed transfer function to uncover the dynamic brain network patterns during the inter-ictal discharging. In addition, an algorithm based on the time-varying outflow of information derived from the network analysis is developed to detect the epileptogenic zone. The analysis performed revealed the time-varying network patterns during different stages of inter-ictal discharging; the epileptogenic zone was activated prior to the discharge onset then worked as the source to propagate the activity to other brain regions. Consistence between the epileptogenic zones detected by our proposed approach and the actual epileptogenic zones proved that time-varying network analysis could not only reveal the underlying neural mechanism of epilepsy, but also function as a useful tool in detecting the epileptogenic zone based on the EEGs in the inter-ictal discharging.

Neuropeptidergic Signaling Partitions Arousal Behaviors in Zebrafish

PubMed Central

Schoppik, David; Shi, Veronica J.; Zimmerman, Steven; Coleman, Haley A.; Greenwood, Joel; Soucy, Edward R.

2014-01-01

Animals modulate their arousal state to ensure that their sensory responsiveness and locomotor activity match environmental demands. Neuropeptides can regulate arousal, but studies of their roles in vertebrates have been constrained by the vast array of neuropeptides and their pleiotropic effects. To overcome these limitations, we systematically dissected the neuropeptidergic modulation of arousal in larval zebrafish. We quantified spontaneous locomotor activity and responsiveness to sensory stimuli after genetically induced expression of seven evolutionarily conserved neuropeptides, including adenylate cyclase activating polypeptide 1b (adcyap1b), cocaine-related and amphetamine-related transcript (cart), cholecystokinin (cck), calcitonin gene-related peptide (cgrp), galanin, hypocretin, and nociceptin. Our study reveals that arousal behaviors are dissociable: neuropeptide expression uncoupled spontaneous activity from sensory responsiveness, and uncovered modality-specific effects upon sensory responsiveness. Principal components analysis and phenotypic clustering revealed both shared and divergent features of neuropeptidergic functions: hypocretin and cgrp stimulated spontaneous locomotor activity, whereas galanin and nociceptin attenuated these behaviors. In contrast, cart and adcyap1b enhanced sensory responsiveness yet had minimal impacts on spontaneous activity, and cck expression induced the opposite effects. Furthermore, hypocretin and nociceptin induced modality-specific differences in responsiveness to changes in illumination. Our study provides the first systematic and high-throughput analysis of neuropeptidergic modulation of arousal, demonstrates that arousal can be partitioned into independent behavioral components, and reveals novel and conserved functions of neuropeptides in regulating arousal. PMID:24573274

Default-Mode Network Functional Connectivity in Aphasia: Therapy-Induced Neuroplasticity

ERIC Educational Resources Information Center

Marcotte, Karine; Perlbarg, Vincent; Marrelec, Guillaume; Benali, Habib; Ansaldo, Ana Ines

2013-01-01

Previous research on participants with aphasia has mainly been based on standard functional neuroimaging analysis. Recent studies have shown that functional connectivity analysis can detect compensatory activity, not revealed by standard analysis. Little is known, however, about the default-mode network in aphasia. In the current study, we studied…

Investigation of summer monsoon rainfall variability in Pakistan

NASA Astrophysics Data System (ADS)

Hussain, Mian Sabir; Lee, Seungho

2016-08-01

This study analyzes the inter-annual and intra-seasonal rainfall variability in Pakistan using daily rainfall data during the summer monsoon season (June to September) recorded from 1980 to 2014. The variability in inter-annual monsoon rainfall ranges from 20 % in northeastern regions to 65 % in southwestern regions of Pakistan. The analysis reveals that the transition of the negative and positive anomalies was not uniform in the investigated dataset. In order to acquire broad observations of the intra-seasonal variability, an objective criterion, the pre-active period, active period and post-active periods of the summer monsoon rainfall have demarcated. The analysis also reveals that the rainfall in June has no significant contribution to the increase in intra-seasonal rainfall in Pakistan. The rainfall has, however, been enhanced in the summer monsoon in August. The rainfall of September demonstrates a sharp decrease, resulting in a high variability in the summer monsoon season. A detailed examination of the intra-seasonal rainfall also reveals frequent amplitude from late July to early August. The daily normal rainfall fluctuates significantly with its maximum in the Murree hills and its minimum in the northwestern Baluchistan.

Photoelectron spectra and biological activity of cinnamic acid derivatives revisited

NASA Astrophysics Data System (ADS)

Novak, Igor; Klasinc, Leo; McGlynn, Sean P.

2018-01-01

The electronic structures of several derivatives of cinnamic acid have been studied by UV photoelectron spectroscopy (UPS) and Green's function quantum chemical calculations. The spectra reveal the presence of dimers in the gas phase for p-coumaric and ferulic acids. The electronic structure analysis has been related to the biological properties of these compounds through the analysis of some structure-activity relationships (SAR).

Transcriptome profiling of a Saccharomyces cerevisiae mutant with a constitutively activated Ras/cAMP pathway.

PubMed

Jones, D L; Petty, J; Hoyle, D C; Hayes, A; Ragni, E; Popolo, L; Oliver, S G; Stateva, L I

2003-12-16

Often changes in gene expression levels have been considered significant only when above/below some arbitrarily chosen threshold. We investigated the effect of applying a purely statistical approach to microarray analysis and demonstrated that small changes in gene expression have biological significance. Whole genome microarray analysis of a pde2Delta mutant, constructed in the Saccharomyces cerevisiae reference strain FY23, revealed altered expression of approximately 11% of protein encoding genes. The mutant, characterized by constitutive activation of the Ras/cAMP pathway, has increased sensitivity to stress, reduced ability to assimilate nonfermentable carbon sources, and some cell wall integrity defects. Applying the Munich Information Centre for Protein Sequences (MIPS) functional categories revealed increased expression of genes related to ribosome biogenesis and downregulation of genes in the cell rescue, defense, cell death and aging category, suggesting a decreased response to stress conditions. A reduced level of gene expression in the unfolded protein response pathway (UPR) was observed. Cell wall genes whose expression was affected by this mutation were also identified. Several of the cAMP-responsive orphan genes, upon further investigation, revealed cell wall functions; others had previously unidentified phenotypes assigned to them. This investigation provides a statistical global transcriptome analysis of the cellular response to constitutive activation of the Ras/cAMP pathway.

Soil ionomic and enzymatic responses and correlations to fertilizations amended with and without organic fertilizer in long-term experiments.

PubMed

Feng, Xumeng; Ling, Ning; Chen, Huan; Zhu, Chen; Duan, Yinghua; Peng, Chang; Yu, Guanghui; Ran, Wei; Shen, Qirong; Guo, Shiwei

2016-04-15

To investigate potential interactions between the soil ionome and enzyme activities affected by fertilization with or without organic fertilizer, soil samples were collected from four long-term experiments over China. Irrespective of variable interactions, fertilization type was the major factor impacting soil ionomic behavior and accounted for 15.14% of the overall impact. Sampling site was the major factor affecting soil enzymatic profile and accounted for 34.25% of the overall impact. The availabilities of Pb, La, Ni, Co, Fe and Al were significantly higher in soil with only chemical fertilizer than the soil with organic amendment. Most of the soil enzyme activities, including α-glucosidase activity, were significantly activated by organic amendment. Network analysis between the soil ionome and the soil enzyme activities was more complex in the organic-amended soils than in the chemical fertilized soils, whereas the network analysis among the soil ions was less complex with organic amendment. Moreover, α-glucosidase was revealed to generally harbor more corrections with the soil ionic availabilities in network. We concluded that some of the soil enzymes activated by organic input can make the soil more vigorous and stable and that the α-glucosidase revealed by this analysis might help stabilize the soil ion availability.

Soil ionomic and enzymatic responses and correlations to fertilizations amended with and without organic fertilizer in long-term experiments

PubMed Central

Feng, Xumeng; Ling, Ning; Chen, Huan; Zhu, Chen; Duan, Yinghua; Peng, Chang; Yu, Guanghui; Ran, Wei; Shen, Qirong; Guo, Shiwei

2016-01-01

To investigate potential interactions between the soil ionome and enzyme activities affected by fertilization with or without organic fertilizer, soil samples were collected from four long-term experiments over China. Irrespective of variable interactions, fertilization type was the major factor impacting soil ionomic behavior and accounted for 15.14% of the overall impact. Sampling site was the major factor affecting soil enzymatic profile and accounted for 34.25% of the overall impact. The availabilities of Pb, La, Ni, Co, Fe and Al were significantly higher in soil with only chemical fertilizer than the soil with organic amendment. Most of the soil enzyme activities, including α-glucosidase activity, were significantly activated by organic amendment. Network analysis between the soil ionome and the soil enzyme activities was more complex in the organic-amended soils than in the chemical fertilized soils, whereas the network analysis among the soil ions was less complex with organic amendment. Moreover, α-glucosidase was revealed to generally harbor more corrections with the soil ionic availabilities in network. We concluded that some of the soil enzymes activated by organic input can make the soil more vigorous and stable and that the α-glucosidase revealed by this analysis might help stabilize the soil ion availability. PMID:27079657

Bioactivity Assessment of Indian Origin-Mangrove Actinobacteria against Candida albicans.

PubMed

Pavan Kumar, J G S; Gomathi, Ajitha; Gothandam, K M; Vasconcelos, Vitor

2018-02-12

Actinobacteria is found to have a potent metabolic activity against pathogens. The present study reveals the assessment of potent antifungal secondary metabolites from actinobacteria isolated from Indian marine mangrove sediments. The samples were collected from the coastal regions of Muthupet, Andaman and the Nicobar Islands. Identification was carried out using 16S rRNA analysis and biosynthetic genes (Polyketide synthase type I/II and Non-ribosomal peptide synthase) were screened. Actinobacteria were assayed for their antifungal activity against 16 clinical Candida albicans and the compound analysis was performed using gas chromatography-mass spectrometry GC-MS. The 31 actinobacterial strains were isolated and 16S rRNA gene sequencing revealed that this ecosystem is rich on actinobacteria, with Streptomyces as the predominant genus. The PCR based screening of biosynthetic genes revealed the presence of PKS-I in six strains, PKS-II in four strains and NRPS in 11 strains. The isolated actinobacteria VITGAP240 and VITGAP241 (two isolates) were found to have a potential antifungal activity against all the tested C. albicans . GC-MS results revealed that the actinobacterial compounds were belonging to heterocyclic, polyketides and peptides. Overall, the strains possess a wide spectrum of antifungal properties which affords the production of significant bioactive metabolites as potential antibiotics.

Bioactivity Assessment of Indian Origin—Mangrove Actinobacteria against Candida albicans

PubMed Central

Pavan Kumar, J. G. S.; Gomathi, Ajitha; Vasconcelos, Vitor

2018-01-01

Actinobacteria is found to have a potent metabolic activity against pathogens. The present study reveals the assessment of potent antifungal secondary metabolites from actinobacteria isolated from Indian marine mangrove sediments. The samples were collected from the coastal regions of Muthupet, Andaman and the Nicobar Islands. Identification was carried out using 16S rRNA analysis and biosynthetic genes (Polyketide synthase type I/II and Non-ribosomal peptide synthase) were screened. Actinobacteria were assayed for their antifungal activity against 16 clinical Candida albicans and the compound analysis was performed using gas chromatography-mass spectrometry GC-MS. The 31 actinobacterial strains were isolated and 16S rRNA gene sequencing revealed that this ecosystem is rich on actinobacteria, with Streptomyces as the predominant genus. The PCR based screening of biosynthetic genes revealed the presence of PKS-I in six strains, PKS-II in four strains and NRPS in 11 strains. The isolated actinobacteria VITGAP240 and VITGAP241 (two isolates) were found to have a potential antifungal activity against all the tested C. albicans. GC-MS results revealed that the actinobacterial compounds were belonging to heterocyclic, polyketides and peptides. Overall, the strains possess a wide spectrum of antifungal properties which affords the production of significant bioactive metabolites as potential antibiotics. PMID:29439535

Skeletal muscle adaptations to microgravity exposure in the mouse.

PubMed

Harrison, B C; Allen, D L; Girten, B; Stodieck, L S; Kostenuik, P J; Bateman, T A; Morony, S; Lacey, D; Leinwand, L A

2003-12-01

To investigate the effects of microgravity on murine skeletal muscle fiber size, muscle contractile protein, and enzymatic activity, female C57BL/6J mice, aged 64 days, were divided into animal enclosure module (AEM) ground control and spaceflight (SF) treatment groups. SF animals were flown on the space shuttle Endeavour (STS-108/UF-1) and subjected to approximately 11 days and 19 h of microgravity. Immunohistochemical analysis of muscle fiber cross-sectional area revealed that, in each of the muscles analyzed, mean muscle fiber cross-sectional area was significantly reduced (P < 0.0001) for all fiber types for SF vs. AEM control. In the soleus, immunohistochemical analysis of myosin heavy chain (MHC) isoform expression revealed a significant increase in the percentage of muscle fibers expressing MHC IIx and MHC IIb (P < 0.05). For the gastrocnemius and plantaris, no significant changes in MHC isoform expression were observed. For the muscles analyzed, no alterations in MHC I or MHC IIa protein expression were observed. Enzymatic analysis of the gastrocnemius revealed a significant decrease in citrate synthase activity in SF vs. AEM control.

Augmenting the activity of antifungal agents against aspergilli using structural analogues of benzoic acid as chemosensitizing agents

USDA-ARS?s Scientific Manuscript database

Structure-activity analysis revealed that antifungal activities of benzoic and gallic acids were increased against strains of Aspergillus flavus, A. fumigatus and A. terreus, causative agents of human aspergillosis, by addition of a methyl, methoxyl or a chloro group at position 4 of the aromatic ri...

Accessible cultural mind-set modulates default mode activity: evidence for the culturally situated brain.

PubMed

Wang, Chenbo; Oyserman, Daphna; Liu, Qiang; Li, Hong; Han, Shihui

2013-01-01

Self-construal priming modulates human behavior and associated neural activity. However, the neural activity associated with the self-construal priming procedure itself remains unknown. It is also unclear whether and how self-construal priming affects neural activity prior to engaging in a particular task. To address this gap, we scanned Chinese adults, using functional magnetic resonance imaging, during self-construal priming and a following resting state. We found that, relative to a calculation task, both interdependent and independent self-construal priming activated the ventral medial prefrontal cortex (MPFC) and the posterior cingulate cortex (PCC). The contrast of interdependent vs. independent self-construal priming also revealed increased activity in the dorsal MPFC and left middle frontal cortex. The regional homogeneity analysis of the resting-state activity revealed increased local synchronization of spontaneous activity in the dorsal MPFC but decreased local synchronization of spontaneous activity in the PCC when contrasting interdependent vs. independent self-construal priming. The functional connectivity analysis of the resting-state activity, however, did not show significant difference in synchronization of activities in remote brain regions between different priming conditions. Our findings suggest that accessible collectivistic/individualistic mind-set induced by self-construal priming is associated with modulations of both task-related and resting-state activity in the default mode network.

Gimme, It's Mine!: Children's Concepts of Ownership as Revealed in Interaction.

ERIC Educational Resources Information Center

Bluebond-Langner, Myra

This investigation probes nursery school activities and children's interactions in relation to private and communal property. Analysis of 27 hours of taped interaction spread over 4 months of participant observation reveals that children attempt to gain access to private property in a different way than they try to obtain access to communal…

Default mode of brain function in monkeys.

PubMed

Mantini, Dante; Gerits, Annelis; Nelissen, Koen; Durand, Jean-Baptiste; Joly, Olivier; Simone, Luciano; Sawamura, Hiromasa; Wardak, Claire; Orban, Guy A; Buckner, Randy L; Vanduffel, Wim

2011-09-07

Human neuroimaging has revealed a specific network of brain regions-the default-mode network (DMN)-that reduces its activity during goal-directed behavior. So far, evidence for a similar network in monkeys is mainly indirect, since, except for one positron emission tomography study, it is all based on functional connectivity analysis rather than activity increases during passive task states. Here, we tested whether a consistent DMN exists in monkeys using its defining property. We performed a meta-analysis of functional magnetic resonance imaging data collected in 10 awake monkeys to reveal areas in which activity consistently decreases when task demands shift from passive tasks to externally oriented processing. We observed task-related spatially specific deactivations across 15 experiments, implying in the monkey a functional equivalent of the human DMN. We revealed by resting-state connectivity that prefrontal and medial parietal regions, including areas 9/46d and 31, respectively, constitute the DMN core, being functionally connected to all other DMN areas. We also detected two distinct subsystems composed of DMN areas with stronger functional connections between each other. These clusters included areas 24/32, 8b, and TPOC and areas 23, v23, and PGm, respectively. Such a pattern of functional connectivity largely fits, but is not completely consistent with anatomical tract tracing data in monkeys. Also, analysis of afferent and efferent connections between DMN areas suggests a multisynaptic network structure. Like humans, monkeys increase activity during passive epochs in heteromodal and limbic association regions, suggesting that they also default to internal modes of processing when not actively interacting with the environment.

Default Mode of Brain Function in Monkeys

PubMed Central

Mantini, Dante; Gerits, Annelis; Nelissen, Koen; Durand, Jean-Baptiste; Joly, Olivier; Simone, Luciano; Sawamura, Hiromasa; Wardak, Claire; Orban, Guy A.; Buckner, Randy L.; Vanduffel, Wim

2013-01-01

Human neuroimaging has revealed a specific network of brain regions—the default-mode network (DMN)—that reduces its activity during goal-directed behavior. So far, evidence for a similar network in monkeys is mainly indirect, since, except for one positron emission tomography study, it is all based on functional connectivity analysis rather than activity increases during passive task states. Here, we tested whether a consistent DMN exists in monkeys using its defining property. We performed a meta-analysis of functional magnetic resonance imaging data collected in 10 awake monkeys to reveal areas in which activity consistently decreases when task demands shift from passive tasks to externally oriented processing. We observed task-related spatially specific deactivations across 15 experiments, implying in the monkey a functional equivalent of the human DMN. We revealed by resting-state connectivity that prefrontal and medial parietal regions, including areas 9/46d and 31, respectively, constitute the DMN core, being functionally connected to all other DMN areas. We also detected two distinct subsystems composed of DMN areas with stronger functional connections between each other. These clusters included areas 24/32, 8b, and TPOC and areas 23, v23, and PGm, respectively. Such a pattern of functional connectivity largely fits, but is not completely consistent with anatomical tract tracing data in monkeys. Also, analysis of afferent and efferent connections between DMN areas suggests a multisynaptic network structure. Like humans, monkeys increase activity during passive epochs in heteromodal and limbic association regions, suggesting that they also default to internal modes of processing when not actively interacting with the environment. PMID:21900574

Neural correlates of social exclusion across ages: A coordinate-based meta-analysis of functional MRI studies.

PubMed

Vijayakumar, Nandita; Cheng, Theresa W; Pfeifer, Jennifer H

2017-06-01

Given the recent surge in functional neuroimaging studies on social exclusion, the current study employed activation likelihood estimation (ALE) based meta-analyses to identify brain regions that have consistently been implicated across different experimental paradigms used to investigate exclusion. We also examined the neural correlates underlying Cyberball, the most commonly used paradigm to study exclusion, as well as differences in exclusion-related activation between developing (7-18 years of age, from pre-adolescence up to late adolescence) and emerging adult (broadly defined as undergraduates, including late adolescence and young adulthood) samples. Results revealed involvement of the bilateral medial prefrontal and posterior cingulate cortices, right precuneus and left ventrolateral prefrontal cortex across the different paradigms used to examine social exclusion; similar activation patterns were identified when restricting the analysis to Cyberball studies. Investigations into age-related effects revealed that ventrolateral prefrontal activations identified in the full sample were driven by (i.e. present in) developmental samples, while medial prefrontal activations were driven by emerging adult samples. In addition, the right ventral striatum was implicated in exclusion, but only in developmental samples. Subtraction analysis revealed significantly greater activation likelihood in striatal and ventrolateral prefrontal clusters in the developmental samples as compared to emerging adults, though the opposite contrast failed to identify any significant regions. Findings integrate the knowledge accrued from functional neuroimaging studies on social exclusion to date, highlighting involvement of lateral prefrontal regions implicated in regulation and midline structures involved in social cognitive and self-evaluative processes across experimental paradigms and ages, as well as limbic structures in developing samples specifically. Copyright © 2017 Elsevier Inc. All rights reserved.

Brain activity across the development of automatic categorization: A comparison of categorization tasks using multi-voxel pattern analysis

PubMed Central

Soto, Fabian A.; Waldschmidt, Jennifer G.; Helie, Sebastien; Ashby, F. Gregory

2013-01-01

Previous evidence suggests that relatively separate neural networks underlie initial learning of rule-based and information-integration categorization tasks. With the development of automaticity, categorization behavior in both tasks becomes increasingly similar and exclusively related to activity in cortical regions. The present study uses multi-voxel pattern analysis to directly compare the development of automaticity in different categorization tasks. Each of three groups of participants received extensive training in a different categorization task: either an information-integration task, or one of two rule-based tasks. Four training sessions were performed inside an MRI scanner. Three different analyses were performed on the imaging data from a number of regions of interest (ROIs). The common patterns analysis had the goal of revealing ROIs with similar patterns of activation across tasks. The unique patterns analysis had the goal of revealing ROIs with dissimilar patterns of activation across tasks. The representational similarity analysis aimed at exploring (1) the similarity of category representations across ROIs and (2) how those patterns of similarities compared across tasks. The results showed that common patterns of activation were present in motor areas and basal ganglia early in training, but only in the former later on. Unique patterns were found in a variety of cortical and subcortical areas early in training, but they were dramatically reduced with training. Finally, patterns of representational similarity between brain regions became increasingly similar across tasks with the development of automaticity. PMID:23333700

Overexpression of Human-Derived DNMT3A Induced Intergenerational Inheritance of Active DNA Methylation Changes in Rat Sperm

PubMed Central

Zheng, Xiaoguo; Li, Zhenhua; Wang, Guishuan; Li, Zhengzheng; Liang, Ajuan; Wang, Hanshu; Dai, Yubing; Huang, Xingxu; Chen, Xuejin; Ma, Yuanwu; Sun, Fei

2017-01-01

DNA methylation is the major focus of studies on paternal epigenetic inheritance in mammals, but most previous studies about inheritable DNA methylation changes are passively induced by environmental factors. However, it is unclear whether the active changes mediated by variations in DNA methyltransferase activity are heritable. Here, we established human-derived DNMT3A (hDNMT3A) transgenic rats to study the effect of hDNMT3A overexpression on the DNA methylation pattern of rat sperm and to investigate whether this actively altered DNA methylation status is inheritable. Our results revealed that hDNMT3A was overexpressed in the testis of transgenic rats and induced genome-wide alterations in the DNA methylation pattern of rat sperm. Among 5438 reliable loci identified with 64 primer-pair combinations using a methylation-sensitive amplification polymorphism method, 28.01% showed altered amplified band types. Among these amplicons altered loci, 68.42% showed an altered DNA methylation status in the offspring of transgenic rats compared with wild-type rats. Further analysis based on loci which had identical DNA methylation status in all three biological replicates revealed that overexpression of hDNMT3A in paternal testis induced hypermethylation in sperm of both genotype-negative and genotype-positive offspring. Among the differentially methylated loci, 34.26% occurred in both positive and negative offspring of transgenic rats, indicating intergenerational inheritance of active DNA methylation changes in the absence of hDNM3A transmission. Furthermore, 75.07% of the inheritable loci were hyper-methylated while the remaining were hypomethylated. Distribution analysis revealed that the DNA methylation variations mainly occurred in introns and intergenic regions. Functional analysis revealed that genes related to differentially methylated loci were involved in a wide range of functions. Finally, this study demonstrated that active DNA methylation changes induced by hDNMT3A expression were intergenerationally inherited by offspring without transmission of the transgene, which provided evidence for the transmission of active endogenous-factors-induced epigenetic variations. PMID:29312436

Molecular Dynamics Analysis Reveals Structural Insights into Mechanism of Nicotine N-Demethylation Catalyzed by Tobacco Cytochrome P450 Mono-Oxygenase

PubMed Central

Wang, Shan; Yang, Shuo; An, Baiyi; Wang, Shichen; Yin, Yuejia; Lu, Yang; Xu, Ying; Hao, Dongyun

2011-01-01

CYP82E4, a cytochrome P450 monooxygenase, has nicotine N-demethylase (NND) activity, which mediates the bioconversion of nicotine into nornicotine in senescing tobacco leaves. Nornicotine is a precursor of the carcinogen, tobacco-specific nitrosamine. CYP82E3 is an ortholog of CYP82E4 with 95% sequence identity, but it lacks NND activity. A recent site-directed mutagenesis study revealed that a single amino acid substitution, i.e., cysteine to tryptophan at the 330 position in the middle of protein, restores the NND activity of CYP82E3 entirely. However, the same amino acid change caused the loss of the NND activity of CYP82E4. To determine the mechanism of the functional turnover of the two molecules, four 3D structures, i.e., the two molecules and their corresponding cys–trp mutants were modeled. The resulting structures exhibited that the mutation site is far from the active site, which suggests that no direct interaction occurs between the two sites. Simulation studies in different biological scenarios revealed that the mutation introduces a conformation drift with the largest change at the F-G loop. The dynamics trajectories analysis using principal component analysis and covariance analysis suggests that the single amino acid change causes the opening and closing of the transfer channels of the substrates, products, and water by altering the motion of the F-G and B-C loops. The motion of helix I is also correlated with the motion of both the F-G loop and the B-C loop and; the single amino acid mutation resulted in the curvature of helix I. These results suggest that the single amino acid mutation outside the active site region may have indirectly mediated the flexibility of the F-G and B-C loops through helix I, causing a functional turnover of the P450 monooxygenase. PMID:21858078

Hormone activation induces nucleosome positioning in vivo

PubMed Central

Belikov, Sergey; Gelius, Birgitta; Almouzni, Geneviève; Wrange, Örjan

2000-01-01

The mouse mammary tumor virus (MMTV) promoter is induced by glucocorticoid hormone. A robust hormone- and receptor-dependent activation could be reproduced in Xenopus laevis oocytes. The homogeneous response in this system allowed a detailed analysis of the transition in chromatin structure following hormone activation. This revealed two novel findings: hormone activation led to the establishment of specific translational positioning of nucleosomes despite the lack of significant positioning in the inactive state; and, in the active promoter, a subnucleosomal particle encompassing the glucocorticoid receptor (GR)-binding region was detected. The presence of only a single GR-binding site was sufficient for the structural transition to occur. Both basal promoter elements and ongoing transcription were dispensable. These data reveal a stepwise process in the transcriptional activation by glucocorticoid hormone. PMID:10698943

Using Spatial Multiple Regression to Identify Intrinsic Connectivity Networks Involved in Working Memory Performance

PubMed Central

Gordon, Evan M.; Stollstorff, Melanie; Vaidya, Chandan J.

2012-01-01

Many researchers have noted that the functional architecture of the human brain is relatively invariant during task performance and the resting state. Indeed, intrinsic connectivity networks (ICNs) revealed by resting-state functional connectivity analyses are spatially similar to regions activated during cognitive tasks. This suggests that patterns of task-related activation in individual subjects may result from the engagement of one or more of these ICNs; however, this has not been tested. We used a novel analysis, spatial multiple regression, to test whether the patterns of activation during an N-back working memory task could be well described by a linear combination of ICNs delineated using Independent Components Analysis at rest. We found that across subjects, the cingulo-opercular Set Maintenance ICN, as well as right and left Frontoparietal Control ICNs, were reliably activated during working memory, while Default Mode and Visual ICNs were reliably deactivated. Further, involvement of Set Maintenance, Frontoparietal Control, and Dorsal Attention ICNs was sensitive to varying working memory load. Finally, the degree of left Frontoparietal Control network activation predicted response speed, while activation in both left Frontoparietal Control and Dorsal Attention networks predicted task accuracy. These results suggest that a close relationship between resting-state networks and task-evoked activation is functionally relevant for behavior, and that spatial multiple regression analysis is a suitable method for revealing that relationship. PMID:21761505

Vector analysis of ecoenzyme activities reveal constraints on coupled C, N and P dynamics

EPA Science Inventory

We developed a quantitative method for estimating resource allocation strategies of microbial communities based on the proportional activities of four, key extracellular enzymes, 1,4-ß-glucosidase (BG), leucine amino-peptidase (LAP), 1,4-ß-N-acetylglucosaminidase (NAG...

Molecular insights into the activity and mechanism of cyanide hydratase enzyme associated with cyanide biodegradation by Serratia marcescens.

PubMed

Kushwaha, Madhulika; Kumar, Virender; Mahajan, Rishi; Bhalla, Tek Chand; Chatterjee, Subhankar; Akhter, Yusuf

2018-05-09

The present study provides molecular insights into the activity and mechanism of cyanide hydratase enzyme associated with degradation of cyanide compounds, using Serratia marcescens RL2b as a model organism. Resting cells harvested after 20 h achieved complete degradation of 12 mmol l - 1 cyanide in approximately 10 h. High-performance liquid chromatography analysis of reaction samples revealed formation of formamide as the only end product, which confirmed the presence of cyanide hydratase activity in S. marcescens RL2b. Comparative structural analysis with the other nitrilase family proteins, which was carried out using a sequence of cyanide hydratase from a phylogenetically related strain S. marcescens WW4, also revealed subtle but significant differences in amino acid residues of the substrate-binding pocket and catalytic triad (Cys-Lys-Glu).

Peptidomic analysis reveals proteolytic activity of kefir microorganisms on bovine milk proteins

PubMed Central

Dallas, David C.; Citerne, Florine; Tian, Tian; Silva, Vitor L. M.; Kalanetra, Karen M.; Frese, Steven A.; Robinson, Randall C.; Mills, David A.; Barile, Daniela

2015-01-01

Scope The microorganisms that make up kefir grains are well known for lactose fermentation, but the extent to which they hydrolyze and consume milk proteins remains poorly understood. Peptidomics technologies were used to examine the proteolytic activity of kefir grains on bovine milk proteins. Methods and results Gel electrophoresis revealed substantial digestion of milk proteins by kefir grains, with mass spectrometric analysis showing the release of 609 protein fragments and alteration of the abundance of >1,500 peptides that derived from 27 milk proteins. Kefir contained 25 peptides identified from the literature as having biological activity, including those with antihypertensive, antimicrobial, immunomodulatory, opioid and anti-oxidative functions. 16S rRNA and shotgun metagenomic sequencing identified the principle taxa in the culture as Lactobacillus species. Conclusion The model kefir sample contained thousands of protein fragments released in part by kefir microorganisms and in part by native milk proteases. PMID:26616950

Peptidomic analysis reveals proteolytic activity of kefir microorganisms on bovine milk proteins.

PubMed

Dallas, David C; Citerne, Florine; Tian, Tian; Silva, Vitor L M; Kalanetra, Karen M; Frese, Steven A; Robinson, Randall C; Mills, David A; Barile, Daniela

2016-04-15

The microorganisms that make up kefir grains are well known for lactose fermentation, but the extent to which they hydrolyze and consume milk proteins remains poorly understood. Peptidomics technologies were used to examine the proteolytic activity of kefir grains on bovine milk proteins. Gel electrophoresis revealed substantial digestion of milk proteins by kefir grains, with mass spectrometric analysis showing the release of 609 protein fragments and alteration of the abundance of >1500 peptides that derived from 27 milk proteins. Kefir contained 25 peptides identified from the literature as having biological activity, including those with antihypertensive, antimicrobial, immunomodulatory, opioid and anti-oxidative functions. 16S rRNA and shotgun metagenomic sequencing identified the principle taxa in the culture as Lactobacillus species. The model kefir sample contained thousands of protein fragments released in part by kefir microorganisms and in part by native milk proteases. Copyright © 2015 Elsevier Ltd. All rights reserved.

Comprehensive Analysis of Temporal Alterations in Cellular Proteome of Bacillus subtilis under Curcumin Treatment

PubMed Central

Reddy, Panga Jaipal; Sinha, Sneha; Ray, Sandipan; Sathe, Gajanan J.; Chatterjee, Aditi; Prasad, T. S. Keshava; Dhali, Snigdha; Srikanth, Rapole; Panda, Dulal; Srivastava, Sanjeeva

2015-01-01

Curcumin is a natural dietary compound with antimicrobial activity against various gram positive and negative bacteria. This study aims to investigate the proteome level alterations in Bacillus subtilis due to curcumin treatment and identification of its molecular/cellular targets to understand the mechanism of action. We have performed a comprehensive proteomic analysis of B. subtilis AH75 strain at different time intervals of curcumin treatment (20, 60 and 120 min after the drug exposure, three replicates) to compare the protein expression profiles using two complementary quantitative proteomic techniques, 2D-DIGE and iTRAQ. To the best of our knowledge, this is the first comprehensive longitudinal investigation describing the effect of curcumin treatment on B. subtilis proteome. The proteomics analysis revealed several interesting targets such UDP-N-acetylglucosamine 1-carboxyvinyltransferase 1, putative septation protein SpoVG and ATP-dependent Clp protease proteolytic subunit. Further, in silico pathway analysis using DAVID and KOBAS has revealed modulation of pathways related to the fatty acid metabolism and cell wall synthesis, which are crucial for cell viability. Our findings revealed that curcumin treatment lead to inhibition of the cell wall and fatty acid synthesis in addition to differential expression of many crucial proteins involved in modulation of bacterial metabolism. Findings obtained from proteomics analysis were further validated using 5-cyano-2,3-ditolyl tetrazolium chloride (CTC) assay for respiratory activity, resazurin assay for metabolic activity and membrane integrity assay by potassium and inorganic phosphate leakage measurement. The gene expression analysis of selected cell wall biosynthesis enzymes has strengthened the proteomics findings and indicated the major effect of curcumin on cell division. PMID:25874956

Comprehensive analysis of temporal alterations in cellular proteome of Bacillus subtilis under curcumin treatment.

PubMed

Reddy, Panga Jaipal; Sinha, Sneha; Ray, Sandipan; Sathe, Gajanan J; Chatterjee, Aditi; Prasad, T S Keshava; Dhali, Snigdha; Srikanth, Rapole; Panda, Dulal; Srivastava, Sanjeeva

2015-01-01

Curcumin is a natural dietary compound with antimicrobial activity against various gram positive and negative bacteria. This study aims to investigate the proteome level alterations in Bacillus subtilis due to curcumin treatment and identification of its molecular/cellular targets to understand the mechanism of action. We have performed a comprehensive proteomic analysis of B. subtilis AH75 strain at different time intervals of curcumin treatment (20, 60 and 120 min after the drug exposure, three replicates) to compare the protein expression profiles using two complementary quantitative proteomic techniques, 2D-DIGE and iTRAQ. To the best of our knowledge, this is the first comprehensive longitudinal investigation describing the effect of curcumin treatment on B. subtilis proteome. The proteomics analysis revealed several interesting targets such UDP-N-acetylglucosamine 1-carboxyvinyltransferase 1, putative septation protein SpoVG and ATP-dependent Clp protease proteolytic subunit. Further, in silico pathway analysis using DAVID and KOBAS has revealed modulation of pathways related to the fatty acid metabolism and cell wall synthesis, which are crucial for cell viability. Our findings revealed that curcumin treatment lead to inhibition of the cell wall and fatty acid synthesis in addition to differential expression of many crucial proteins involved in modulation of bacterial metabolism. Findings obtained from proteomics analysis were further validated using 5-cyano-2,3-ditolyl tetrazolium chloride (CTC) assay for respiratory activity, resazurin assay for metabolic activity and membrane integrity assay by potassium and inorganic phosphate leakage measurement. The gene expression analysis of selected cell wall biosynthesis enzymes has strengthened the proteomics findings and indicated the major effect of curcumin on cell division.

Extending the Constructs of Active Learning: Implications for Teachers' Pedagogy and Practice

ERIC Educational Resources Information Center

Drew, Valerie; Mackie, Lorele

2011-01-01

Active learning is a pedagogical construct widely appealed to within the global discourse of lifelong learning. However, an examination of the literature reveals a lack of clarity and consensus as to its meaning. This article provides a critical analysis of a range of dimensions underpinning the concept of active learning including policy…

Analysis of model replication origins in Drosophila reveals new aspects of the chromatin landscape and its relationship to origin activity and the prereplicative complex

PubMed Central

Liu, Jun; McConnell, Kristopher; Dixon, Michael; Calvi, Brian R.

2012-01-01

Epigenetic regulation exerts a major influence on origins of DNA replication during development. The mechanisms for this regulation, however, are poorly defined. We showed previously that acetylation of nucleosomes regulates the origins that mediate developmental gene amplification during Drosophila oogenesis. Here we show that developmental activation of these origins is associated with acetylation of multiple histone lysines. Although these modifications are not unique to origin loci, we find that the level of acetylation is higher at the active origins and quantitatively correlated with the number of times these origins initiate replication. All of these acetylation marks were developmentally dynamic, rapidly increasing with origin activation and rapidly declining when the origins shut off and neighboring promoters turn on. Fine-scale analysis of the origins revealed that both hyperacetylation of nucleosomes and binding of the origin recognition complex (ORC) occur in a broad domain and that acetylation is highest on nucleosomes adjacent to one side of the major site of replication initiation. It was surprising to find that acetylation of some lysines depends on binding of ORC to the origin, suggesting that multiple histone acetyltransferases may be recruited during origin licensing. Our results reveal new insights into the origin epigenetic landscape and lead us to propose a chromatin switch model to explain the coordination of origin and promoter activity during development. PMID:22049023

Joint cross-correlation analysis reveals complex, time-dependent functional relationship between cortical neurons and arm electromyograms

PubMed Central

Zhuang, Katie Z.; Lebedev, Mikhail A.

2014-01-01

Correlation between cortical activity and electromyographic (EMG) activity of limb muscles has long been a subject of neurophysiological studies, especially in terms of corticospinal connectivity. Interest in this issue has recently increased due to the development of brain-machine interfaces with output signals that mimic muscle force. For this study, three monkeys were implanted with multielectrode arrays in multiple cortical areas. One monkey performed self-timed touch pad presses, whereas the other two executed arm reaching movements. We analyzed the dynamic relationship between cortical neuronal activity and arm EMGs using a joint cross-correlation (JCC) analysis that evaluated trial-by-trial correlation as a function of time intervals within a trial. JCCs revealed transient correlations between the EMGs of multiple muscles and neural activity in motor, premotor and somatosensory cortical areas. Matching results were obtained using spike-triggered averages corrected by subtracting trial-shuffled data. Compared with spike-triggered averages, JCCs more readily revealed dynamic changes in cortico-EMG correlations. JCCs showed that correlation peaks often sharpened around movement times and broadened during delay intervals. Furthermore, JCC patterns were directionally selective for the arm-reaching task. We propose that such highly dynamic, task-dependent and distributed relationships between cortical activity and EMGs should be taken into consideration for future brain-machine interfaces that generate EMG-like signals. PMID:25210153

The role of ligands on the equilibria between functional states of a G protein-coupled receptor.

PubMed

Kim, Tae Hun; Chung, Ka Young; Manglik, Aashish; Hansen, Alexandar L; Dror, Ron O; Mildorf, Thomas J; Shaw, David E; Kobilka, Brian K; Prosser, R Scott

2013-06-26

G protein-coupled receptors exhibit a wide variety of signaling behaviors in response to different ligands. When a small label was incorporated on the cytosolic interface of transmembrane helix 6 (Cys-265), (19)F NMR spectra of the β2 adrenergic receptor (β2AR) reconstituted in maltose/neopentyl glycol detergent micelles revealed two distinct inactive states, an activation intermediate state en route to activation, and, in the presence of a G protein mimic, a predominant active state. Analysis of the spectra as a function of temperature revealed that for all ligands, the activation intermediate is entropically favored and enthalpically disfavored. β2AR enthalpy changes toward activation are notably lower than those observed with rhodopsin, a likely consequence of basal activity and the fact that the ionic lock and other interactions stabilizing the inactive state of β2AR are weaker. Positive entropy changes toward activation likely reflect greater mobility (configurational entropy) in the cytoplasmic domain, as confirmed through an order parameter analysis. Ligands greatly influence the overall changes in enthalpy and entropy of the system and the corresponding changes in population and amplitude of motion of given states, suggesting a complex landscape of states and substates.

Genome Sequence of Enterococcus faecium Strain ICIS 96 Demonstrating Intermicrobial Antagonism Associated with Bacteriocin Production.

PubMed

Pashkova, Tatiana M; Vasilchenko, Alexey S; Khlopko, Yuriy A; Kochkina, Elena E; Kartashova, Olga L; Sycheva, Maria V

2018-03-08

We report here the complete genome sequence of Enterococcus faecium strain ICIS 96, which was isolated from the feces of a horse. Bacteriological characterization of strain ICIS 96 revealed the absence of pathogenicity factors, while its spectrum of antagonistic activity was found to be broad, having activities associated with both Gram-positive and Gram-negative bacteria. Analysis of the E. faecium ICIS 96 genome revealed five genes associated with antimicrobial activity (enterocin [ent] A, ent B, lactobin A/cerein 7b, and ent L50 A/B). No genes that correlate with human pathogenicity were identified. Copyright © 2018 Pashkova et al.

Genome Sequence of Enterococcus faecium Strain ICIS 96 Demonstrating Intermicrobial Antagonism Associated with Bacteriocin Production

PubMed Central

Pashkova, Tatiana M.; Vasilchenko, Alexey S.; Khlopko, Yuriy A.; Kochkina, Elena E.; Kartashova, Olga L.

2018-01-01

ABSTRACT We report here the complete genome sequence of Enterococcus faecium strain ICIS 96, which was isolated from the feces of a horse. Bacteriological characterization of strain ICIS 96 revealed the absence of pathogenicity factors, while its spectrum of antagonistic activity was found to be broad, having activities associated with both Gram-positive and Gram-negative bacteria. Analysis of the E. faecium ICIS 96 genome revealed five genes associated with antimicrobial activity (enterocin [ent] A, ent B, lactobin A/cerein 7b, and ent L50 A/B). No genes that correlate with human pathogenicity were identified. PMID:29519833

Natural and Semisynthetic Analogues of Manadoperoxide B Reveal New Structural Requirements for Trypanocidal Activity

PubMed Central

Chianese, Giuseppina; Scala, Fernando; Calcinai, Barbara; Cerrano, Carlo; Dien, Henny A.; Kaiser, Marcel; Tasdemir, Deniz; Taglialatela-Scafati, Orazio

2013-01-01

Chemical analysis of the Indonesian sponge Plakortis cfr. lita afforded two new analogues of the potent trypanocidal agent manadoperoxide B (1), namely 12-isomanadoperoxide B (2) and manadoperoxidic acid B (3). These compounds were isolated along with a new short chain dicarboxylate monoester (4), bearing some interesting relationships with the polyketide endoperoxides found in this sponge. Some semi-synthetic analogues of manadoperoxide B (6–8) were prepared and evaluated for antitrypanosomal activity and cytotoxicity. These studies revealed crucial structure–activity relationships that should be taken into account in the design of optimized and simplified endoperoxyketal trypanocidal agents. PMID:23989650

[Revealing of tuberculosis in an infectious diseases hospital of a megalopolis].

PubMed

Malashenkov, E A; Ivanovskiĭ, V B

2007-01-01

The advisory work of the phthisiatrician in an infectious diseases hospital was analyzed; the analysis revealed that in 2005 tuberculose changes of various degrees of activity had been revealed in 42.5% of examined patients, and 32.1% of them were subjects in whom tuberculosis of diferent localizations had been revealed for the first time. In 43.2% of the latter subjects, the reasons for hospitalization were "clinical masks" of tuberculose process (influenza, acute respiratory viral disease), while 48.6% were hospitalized for gastrointestinal infections and viral hepatitis. In 20.7% of cases tuberculosis was combined with HIV infection. In the infectious diseases hospital, 16.2% of patients with active tuberculosis died. Among the patients treated in the infectious diseases hospital during one year, the proportion of patients with active tuberculosis was 1.44%, the proportion of those in whom the process was revealed for the first time, was 0.75%. In Botkin infectious diseases hospital, there were approximately 6% of patients in whom tuberculose process was revealed for the first time in Saint Petersburg. The peculiarities of this group of patients in an infectious diseases hospital require not only tuberculose alertness, but also reinforcement of phthisiatric, radiological, and laboratory services.

Thermodynamic coupling between activation and inactivation gating in potassium channels revealed by free energy molecular dynamics simulations.

PubMed

Pan, Albert C; Cuello, Luis G; Perozo, Eduardo; Roux, Benoît

2011-12-01

The amount of ionic current flowing through K(+) channels is determined by the interplay between two separate time-dependent processes: activation and inactivation gating. Activation is concerned with the stimulus-dependent opening of the main intracellular gate, whereas inactivation is a spontaneous conformational transition of the selectivity filter toward a nonconductive state occurring on a variety of timescales. A recent analysis of multiple x-ray structures of open and partially open KcsA channels revealed the mechanism by which movements of the inner activation gate, formed by the inner helices from the four subunits of the pore domain, bias the conformational changes at the selectivity filter toward a nonconductive inactivated state. This analysis highlighted the important role of Phe103, a residue located along the inner helix, near the hinge position associated with the opening of the intracellular gate. In the present study, we use free energy perturbation molecular dynamics simulations (FEP/MD) to quantitatively elucidate the thermodynamic basis for the coupling between the intracellular gate and the selectivity filter. The results of the FEP/MD calculations are in good agreement with experiments, and further analysis of the repulsive, van der Waals dispersive, and electrostatic free energy contributions reveals that the energetic basis underlying the absence of inactivation in the F103A mutation in KcsA is the absence of the unfavorable steric interaction occurring with the large Ile100 side chain in a neighboring subunit when the intracellular gate is open and the selectivity filter is in a conductive conformation. Macroscopic current analysis shows that the I100A mutant indeed relieves inactivation in KcsA, but to a lesser extent than the F103A mutant.

Simulation analysis of capacity and performance improvement in wastewater treatment plants: Case study of Alexandria eastern plant

NASA Astrophysics Data System (ADS)

Moursy, Aly; Sorour, Mohamed T.; Moustafa, Medhat; Elbarqi, Walid; Fayd, Mai; Elreedy, Ahmed

2018-05-01

This study concerns the upgrading of a real domestic wastewater treatment plant (WWTP) supported by simulation. The main aims of this work are to: (1) decide between two technologies to improve WWTP capacity and its nitrogen removal efficiency; membrane bioreactor (MBR) and integrated fixed film activated sludge (IFAS), and (2) perform a cost estimation analysis for the two proposed solutions. The model used was calibrated based on data from the existing WWTP, namely, Eastern plant and located in Alexandria, Egypt. The activated sludge model No. 1 (ASM1) was considered in the model analysis by GPS-X 7 software. Steady-state analysis revealed that high performances corresponded to high compliance with Egyptian standards were achieved by the two techniques; however, MBR was better. Nonetheless, the two systems showed poor nitrogen removal efficiency according to the current situation, which reveals that the plant needs a modification to add an anaerobic treatment unit before the aerobic zone.

Analysis of Normal Human Mammary Epigenomes Reveals Cell-Specific Active Enhancer States and Associated Transcription Factor Networks.

PubMed

Pellacani, Davide; Bilenky, Misha; Kannan, Nagarajan; Heravi-Moussavi, Alireza; Knapp, David J H F; Gakkhar, Sitanshu; Moksa, Michelle; Carles, Annaick; Moore, Richard; Mungall, Andrew J; Marra, Marco A; Jones, Steven J M; Aparicio, Samuel; Hirst, Martin; Eaves, Connie J

2016-11-15

The normal adult human mammary gland is a continuous bilayered epithelial system. Bipotent and myoepithelial progenitors are prominent and unique components of the outer (basal) layer. The inner (luminal) layer includes both luminal-restricted progenitors and a phenotypically separable fraction that lacks progenitor activity. We now report an epigenomic comparison of these three subsets with one another, with their associated stromal cells, and with three immortalized, non-tumorigenic human mammary cell lines. Each genome-wide analysis contains profiles for six histone marks, methylated DNA, and RNA transcripts. Analysis of these datasets shows that each cell type has unique features, primarily within genomic regulatory regions, and that the cell lines group together. Analyses of the promoter and enhancer profiles place the luminal progenitors in between the basal cells and the non-progenitor luminal subset. Integrative analysis reveals networks of subset-specific transcription factors. Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.

Correlation between species-specific metabolite profiles and bioactivities of blueberries (Vaccinium spp.).

PubMed

Lee, Sarah; Jung, Eun Sung; Do, Seon-Gil; Jung, Ga-Young; Song, Gwanpil; Song, Jung-Min; Lee, Choong Hwan

2014-03-05

Metabolite profiling of three blueberry species (Vaccinium bracteatum Thunb., V. oldhamii Miquel., and V. corymbosum L.) was performed using gas chromatography-time-of-flight-mass spectrometry (GC-TOF-MS) and ultraperformance liquid chromatography-quadrupole-time-of-flight-mass spectrometry (UPLC-Q-TOF-MS) combined multivariate analysis. Partial least-squares discriminant analysis clearly showed metabolic differences among species. GC-TOF-MS analysis revealed significant differences in amino acids, organic acids, fatty acids, sugars, and phenolic acids among the three blueberry species. UPLC-Q-TOF-MS analysis indicated that anthocyanins were the major metabolites distinguishing V. bracteatum from V. oldhamii. The contents of anthocyanins such as glycosides of cyanidin were high in V. bracteatum, while glycosides of delphinidin, petunidin, and malvidin were high in V. oldhamii. Antioxidant activities assessed using ABTS and DPPH assays showed the greatest activity in V. oldhamii and revealed the highest correlation with total phenolic, total flavonoid, and total anthocyanin contents and their metabolites.

Antioxidant properties of different edible mushroom species and increased bioconversion efficiency of Pleurotus eryngii using locally available casing materials.

PubMed

Mishra, K K; Pal, R S; Arunkumar, R; Chandrashekara, C; Jain, S K; Bhatt, J C

2013-06-01

Total phenolics, radical scavenging activity (RSA) on DPPH, ascorbic acid content and chelating activity on Fe(2+) of Pleurotus citrinopileatus, Pleurotus djamor, Pleurotus eryngii, Pleurotus flabellatus, Pleurotus florida, Pleurotus ostreatus, Pleurotus sajor-caju and Hypsizygus ulmarius have been evaluated. The assayed mushrooms contained 3.94-21.67 mg TAE of phenolics, 13.63-69.67% DPPH scavenging activity, 3.76-6.76 mg ascorbic acid and 60.25-82.7% chelating activity. Principal Component Analysis (PCA) revealed that significantly higher total phenolics, RSA on DPPH and growth/day was present in P. eryngii whereas P. citrinopileatus showed higher ascorbic acid and chelating activity. Agglomerative hierarchical clustering analysis revealed that studied mushroom species fall into two clusters; Cluster I included P. djamor, P. eryngii and P. flabellatus, while Cluster II included H. ulmarius, P. sajor-caju, P. citrinopileatus, P. ostreatus and P. florida. Enhanced yield of P. eryngii was achieved on spent compost casing material. Use of casing materials enhanced yield by 21-107% over non-cased substrate. Copyright © 2012 Elsevier Ltd. All rights reserved.

MODULATION OF EASTERN OYSTER HEMOCYTE ACTIVITIES BY PERKINSUS MARINUS EXTRACELLULAR PROTEINS

EPA Science Inventory

The oyster pathogen Perkinsus marinusproduces many extracellular proteins (ECP) in vitro. Analysis of this ECP revealed a battery of hydrolytic enzymes. Some of these enzymes are known to modulate the activity of host defense cells. Although information on the effects of P. marin...

Aberrant AKT activation drives well-differentiated liposarcoma

PubMed Central

Gutierrez, Alejandro; Snyder, Eric L.; Marino-Enriquez, Adrian; Zhang, Yi-Xiang; Sioletic, Stefano; Kozakewich, Elena; Grebliunaite, Ruta; Ou, Wen-bin; Sicinska, Ewa; Raut, Chandrajit P.; Demetri, George D.; Perez-Atayde, Antonio R.; Wagner, Andrew J.; Fletcher, Jonathan A.; Fletcher, Christopher D. M.; Look, A. Thomas

2011-01-01

Well-differentiated liposarcoma (WDLPS), one of the most common human sarcomas, is poorly responsive to radiation and chemotherapy, and the lack of animal models suitable for experimental analysis has seriously impeded functional investigation of its pathobiology and development of effective targeted therapies. Here, we show that zebrafish expressing constitutively active Akt2 in mesenchymal progenitors develop WDLPS that closely resembles the human disease. Tumor incidence rates were 8% in p53 wild-type zebrafish, 6% in p53 heterozygotes, and 29% in p53-homozygous mutant zebrafish (P = 0.013), indicating that aberrant Akt activation collaborates with p53 mutation in WDLPS pathogenesis. Analysis of primary clinical specimens of WDLPS, and of the closely related dedifferentiated liposarcoma (DDLPS) subtype, revealed immunohistochemical evidence of AKT activation in 27% of cases. Western blot analysis of a panel of cell lines derived from patients with WDLPS or DDLPS revealed robust AKT phosphorylation in all cell lines examined, even when these cells were cultured in serum-free media. Moreover, BEZ235, a small molecule inhibitor of PI3K and mammalian target of rapamycin that effectively inhibits AKT activation in these cells, impaired viability at nanomolar concentrations. Our findings are unique in providing an animal model to decipher the molecular pathogenesis of WDLPS, and implicate AKT as a previously unexplored therapeutic target in this chemoresistant sarcoma. PMID:21930930

Emotion processing in the visual brain: a MEG analysis.

PubMed

Peyk, Peter; Schupp, Harald T; Elbert, Thomas; Junghöfer, Markus

2008-06-01

Recent functional magnetic resonance imaging (fMRI) and event-related brain potential (ERP) studies provide empirical support for the notion that emotional cues guide selective attention. Extending this line of research, whole head magneto-encephalogram (MEG) was measured while participants viewed in separate experimental blocks a continuous stream of either pleasant and neutral or unpleasant and neutral pictures, presented for 330 ms each. Event-related magnetic fields (ERF) were analyzed after intersubject sensor coregistration, complemented by minimum norm estimates (MNE) to explore neural generator sources. Both streams of analysis converge by demonstrating the selective emotion processing in an early (120-170 ms) and a late time interval (220-310 ms). ERF analysis revealed that the polarity of the emotion difference fields was reversed across early and late intervals suggesting distinct patterns of activation in the visual processing stream. Source analysis revealed the amplified processing of emotional pictures in visual processing areas with more pronounced occipito-parieto-temporal activation in the early time interval, and a stronger engagement of more anterior, temporal, regions in the later interval. Confirming previous ERP studies showing facilitated emotion processing, the present data suggest that MEG provides a complementary look at the spread of activation in the visual processing stream.

Draft whole genome sequence of groundnut stem rot fungus Athelia rolfsii revealing genetic architect of its pathogenicity and virulence.

PubMed

Iquebal, M A; Tomar, Rukam S; Parakhia, M V; Singla, Deepak; Jaiswal, Sarika; Rathod, V M; Padhiyar, S M; Kumar, Neeraj; Rai, Anil; Kumar, Dinesh

2017-07-13

Groundnut (Arachis hypogaea L.) is an important oil seed crop having major biotic constraint in production due to stem rot disease caused by fungus, Athelia rolfsii causing 25-80% loss in productivity. As chemical and biological combating strategies of this fungus are not very effective, thus genome sequencing can reveal virulence and pathogenicity related genes for better understanding of the host-parasite interaction. We report draft assembly of Athelia rolfsii genome of ~73 Mb having 8919 contigs. Annotation analysis revealed 16830 genes which are involved in fungicide resistance, virulence and pathogenicity along with putative effector and lethal genes. Secretome analysis revealed CAZY genes representing 1085 enzymatic genes, glycoside hydrolases, carbohydrate esterases, carbohydrate-binding modules, auxillary activities, glycosyl transferases and polysaccharide lyases. Repeat analysis revealed 11171 SSRs, LTR, GYPSY and COPIA elements. Comparative analysis with other existing ascomycotina genome predicted conserved domain family of WD40, CYP450, Pkinase and ABC transporter revealing insight of evolution of pathogenicity and virulence. This study would help in understanding pathogenicity and virulence at molecular level and development of new combating strategies. Such approach is imperative in endeavour of genome based solution in stem rot disease management leading to better productivity of groundnut crop in tropical region of world.

Photoelectron spectra and biological activity of cinnamic acid derivatives revisited.

PubMed

Novak, Igor; Klasinc, Leo; McGlynn, Sean P

2018-01-15

The electronic structures of several derivatives of cinnamic acid have been studied by UV photoelectron spectroscopy (UPS) and Green's function quantum chemical calculations. The spectra reveal the presence of dimers in the gas phase for p-coumaric and ferulic acids. The electronic structure analysis has been related to the biological properties of these compounds through the analysis of some structure-activity relationships (SAR). Copyright © 2017 Elsevier B.V. All rights reserved.

Canada's Physical Activity Guide: examining print-based material for motivating physical activity in the workplace.

PubMed

Plotnikoff, Ronald C; Todosijczuk, Ivan; Johnson, Steven T; Karunamuni, Nandini

2012-01-01

The authors conducted a secondary analysis on 202 adults from the Physical Activity Workplace Study. The aim of this analysis was to examine demographic characteristics associated with reading Canada's Physical Activity Guide (CPAG), being motivated by the guide, and whether participants in the Physical Activity Workplace Study who read the CPAG increased their physical activity levels over 1 year. Results revealed that less than 50% of participants read the full version of CPAG, and less than 10% were motivated by it. The CPAG also appears to be more appealing to and effective for women than for men. Although the CPAG had some influence in increasing mild physical activity levels in a workplace sample, there was also a decrease in physical activity levels among some members of the group. Overall, the effectiveness of CPAG was not substantial, and the findings of this analysis could help guide future targeted intervention materials and programs.

Multi-element analysis of emeralds and associated rocks by k(o) neutron activation analysis

PubMed

Acharya; Mondal; Burte; Nair; Reddy; Reddy; Reddy; Manohar

2000-12-01

Multi-element analysis was carried out in natural emeralds, their associated rocks and one sample of beryl obtained from Rajasthan, India. The concentrations of 21 elements were assayed by Instrumental Neutron Activation Analysis using the k0 method (k0 INAA method) and high-resolution gamma ray spectrometry. The data reveal the segregation of some elements from associated (trapped and host) rocks to the mineral beryl forming the gemstones. A reference rock standard of the US Geological Survey (USGS BCR-1) was also analysed as a control of the method.

Lignin metabolism involves Botrytis cinerea BcGs1- induced defense response in tomato.

PubMed

Yang, Chenyu; Liang, Yingbo; Qiu, Dewen; Zeng, Hongmei; Yuan, Jingjing; Yang, Xiufen

2018-06-04

BcGs1, a cell wall-degrading enzyme (CWDE), was originally derived from Botrytis cinerea. Our previous study revealed that BcGs1 could trigger defense responses and protect plants against various pathogens. We researched the defense response mechanism underlying this BcGs1 elicitation in tomato. We revealed that the two domains were required for BcGs1's full necrosis activity. According to analysis and quantitative real-time PCR of the up-regulated proteins and genes filtered by iTRAQ-based quantitative proteome approach, oxidative metabolism and phenylpropanoid metabolism were speculated to be involved in BcGs1-triggered defense response in tomato. Furthermore, experimental evidence showed that BcGs1 triggered reactive oxygen species (ROS) burst and increased the level of phenylalanine-ammonia lyase (PAL) and peroxidase (POD) enzyme activity, as well as lignin accumulation. Moreover, histochemical analysis revealed that infiltration of BcGs1 in tomato leaves exhibited cell wall thickening compared with untreated plants. The results suggested that BcGs1 activated the basal defense response included lignin metabolism contributed to BcGs1-induced resistance to Botrytis. cinerea infection in tomato.

Correlates of Successful Aging: Are They Universal?

ERIC Educational Resources Information Center

Litwin, Howard

2005-01-01

The analysis compared differing correlates of life satisfaction among three diverse population groups in Israel, examining background and health status variables, social environment factors, and activity indicators. Multiple regression analysis revealed that veteran Jewish-Israelis (n = 2,043) had the largest set of predictors, the strongest of…

Transcriptomic sequencing reveals a set of unique genes activated by butyrate-induced histone modification

USDA-ARS?s Scientific Manuscript database

Butyrate is a nutritional element with strong epigenetic regulatory activity as an inhibitor of histone deacetylases (HDACs). Based on the analysis of differentially expressed genes induced by butyrate in the bovine epithelial cell using deep RNA-sequencing technology (RNA-seq), a set of unique gen...

Black Educational Activism for Community Empowerment: International Leadership Perspectives

ERIC Educational Resources Information Center

Wilson, Camille; Johnson, Lauri

2015-01-01

This article discusses themes emerging from studies of Black educational activism conducted in London, Toronto, and Detroit. An analysis of narrative data reveals that Black educational activists resist racism and other forms of oppression; act as border crossers and/or boundary spanners as they navigate complex community-based, institutional, and…

HGF/c-Met related activation of β-catenin in hepatoblastoma

PubMed Central

2011-01-01

Background Activation of beta-catenin is a hallmark of hepatoblastoma (HB) and appears to play a crucial role in its pathogenesis. While aberrant accumulation of the beta-catenin is a common event in HB, mutations or deletions in CTNNB1 (beta-catenin gene) do not always account for the high frequency of protein expression. In this study we have investigated alternative activation of beta-catenin by HGF/c-Met signaling in a large cohort of 98 HB patients enrolled in the SIOPEL-3 clinical trial. Methods We performed immunohistochemistry, using antibodies to total beta-catenin and tyrosine654-phosphorylated beta-catenin, which is a good surrogate marker of HGF/c-Met activation. CTNNB1 mutation analysis was also carried out on all samples. We also investigated beta-catenin pathway activation in two liver cancer cell lines, HuH-6 and HuH-7. Results Aberrant beta-catenin expression was seen in the cytoplasm and/or nucleus of 87% of tumour samples. Our results also revealed a large subset of HB, 83%, with cytoplasmic expression of tyrosine654-phosphorylated beta-catenin and 30% showing additional nuclear accumulation. Sequence analysis revealed mutations in 15% of our cohort. Statistical analysis showed an association between nuclear expression of c-Met-activated beta-catenin and wild type CTNNB1 (P-value = 0.015). Analysis of total beta-catenin and Y654-beta-catenin in response to HGF activation in the cell lines, mirrors that observed in our HB tumour cohort. Results We identified a significant subset of hepatoblastoma patients for whom targeting of the c-Met pathway may be a treatment option and also demonstrate distinct mechanisms of beta-catenin activation in HB. PMID:21992464

Molecular details of secretory phospholipase A2 from flax (Linum usitatissimum L.) provide insight into its structure and function.

PubMed

Gupta, Payal; Dash, Prasanta K

2017-09-11

Secretory phospholipase A 2 (sPLA 2 ) are low molecular weight proteins (12-18 kDa) involved in a suite of plant cellular processes imparting growth and development. With myriad roles in physiological and biochemical processes in plants, detailed analysis of sPLA 2 in flax/linseed is meagre. The present work, first in flax, embodies cloning, expression, purification and molecular characterisation of two distinct sPLA 2 s (I and II) from flax. PLA 2 activity of the cloned sPLA 2 s were biochemically assayed authenticating them as bona fide phospholipase A 2 . Physiochemical properties of both the sPLA 2 s revealed they are thermostable proteins requiring di-valent cations for optimum activity.While, structural analysis of both the proteins revealed deviations in the amino acid sequence at C- & N-terminal regions; hydropathic study revealed LusPLA 2 I as a hydrophobic protein and LusPLA 2 II as a hydrophilic protein. Structural analysis of flax sPLA 2 s revealed that secondary structure of both the proteins are dominated by α-helix followed by random coils. Modular superimposition of LusPLA 2 isoforms with rice sPLA 2 confirmed monomeric structural preservation among plant phospholipase A 2 and provided insight into structure of folded flax sPLA 2 s.

Single-trial EEG-informed fMRI analysis of emotional decision problems in hot executive function.

PubMed

Guo, Qian; Zhou, Tiantong; Li, Wenjie; Dong, Li; Wang, Suhong; Zou, Ling

2017-07-01

Executive function refers to conscious control in psychological process which relates to thinking and action. Emotional decision is a part of hot executive function and contains emotion and logic elements. As a kind of important social adaptation ability, more and more attention has been paid in recent years. Gambling task can be well performed in the study of emotional decision. As fMRI researches focused on gambling task show not completely consistent brain activation regions, this study adopted EEG-fMRI fusion technology to reveal brain neural activity related with feedback stimuli. In this study, an EEG-informed fMRI analysis was applied to process simultaneous EEG-fMRI data. First, relative power-spectrum analysis and K-means clustering method were performed separately to extract EEG-fMRI features. Then, Generalized linear models were structured using fMRI data and using different EEG features as regressors. The results showed that in the win versus loss stimuli, the activated regions almost covered the caudate, the ventral striatum (VS), the orbital frontal cortex (OFC), and the cingulate. Wide activation areas associated with reward and punishment were revealed by the EEG-fMRI integration analysis than the conventional fMRI results, such as the posterior cingulate and the OFC. The VS and the medial prefrontal cortex (mPFC) were found when EEG power features were performed as regressors of GLM compared with results entering the amplitudes of feedback-related negativity (FRN) as regressors. Furthermore, the brain region activation intensity was the strongest when theta-band power was used as a regressor compared with the other two fusion results. The EEG-based fMRI analysis can more accurately depict the whole-brain activation map and analyze emotional decision problems.

Garlic, green tea and turmeric extracts-mediated green synthesis of silver nanoparticles: Phytochemical, antioxidant and in vitro cytotoxicity studies.

PubMed

Arumai Selvan, D; Mahendiran, D; Senthil Kumar, R; Kalilur Rahiman, A

2018-03-01

Phyto-synthesis of silver nanoparticles (AgNPs) was achieved using aqueous garlic, green tea and turmeric extracts, and characterized by different spectroscopic techniques. Phytochemical analysis revealed the presence of rich amount of biochemicals in these extracts, which serve as reducing and capping agents for converting silver nitrate into AgNPs. FT IR spectroscopy confirmed the role of biomolecules in the bioreduction and efficient stabilization of AgNPs. UV-Vis DRS spectra showed a band around 450 nm characteristics of AgNPs. XRD patterns revealed the crystalline nature of the synthesized AgNPs with fcc structure. SEM and TEM analysis revealed the spherical shape of the synthesized AgNPs with an average particle size of 8 nm. EDX analysis confirmed the purity of the synthesized AgNPs with a strong signal at 3.2 keV. The antioxidant activity was assessed by ABTS, DPPH, p-NDA, H 2 O 2 and DMSO scavenging assays, in which the AgNPs synthesized using green method showed remarkable activity with respect to the standard antioxidants ascorbic acid and rutin. In vitro cytotoxicity activity was tested on four cancer cell lines such as human breast adenocarcinoma (MCF-7), cervical (HeLa), epithelioma (Hep-2) and lung (A549) along with one normal human dermal fibroblasts (NHDF) cell line. The AgNPs synthesized using turmeric extract exhibits excellent antioxidant and cytotoxicity activity compared to that synthesized using other extracts. Copyright © 2018 Elsevier B.V. All rights reserved.

Dipeptidyl peptidase-II from probiotic Pediococcus acidilactici: Purification and functional characterization.

PubMed

Gandhi, Dimpi; Chanalia, Preeti; Attri, Pooja; Dhanda, Suman

2016-12-01

Dipeptidylpeptidase-II (DPP-II, E.C. 3.4.14.2), an exopeptidase was purified 15.4 fold with specific activity and yield of 15.4U/mg/mL and 14.68% respectively by a simple two step procedure from a probiotic Pediococcus acidilactici. DPP-II is 38.7KDa homodimeric serine peptidase with involvement of His and subunit mass of 18.9KDa. The enzyme exhibited optimal activity at pH 7.0 and 37°C with activation energy of 24.97kJ/mol. The enzyme retained more than 90% activity upto 50°C thus adding industrial importance. DPP-II hydrolysed Lys-Ala-4mβNA with K M of 50μM and V max of 30.8nmol/mL/min. In-silico characterization studies of DPP-II on the basis of peptide fragments obtained by MALDI-TOF revealed an evolutionary relationship between DPP-II of prokaryotes and phosphate binding proteins. Secondary and three-dimensional structure of enzyme was also deduced by in-silico approach. Functional studies of DPP-II by TLC and HPLC-analysis of collagen degraded products revealed that enzyme action released free amino acids and other metabolites. Microscopic and SDS-PAGE analysis of enzyme treated analysis of chicken's chest muscle (meat) hydrolysis revealed change and hydrolysis of myofibrils. This may affect the flavor and texture of meat thereby suggesting its role in meat tenderization. Being a protein of LAB (Lactic acid bacteria), it is also expected to be safe. Copyright © 2016 Elsevier B.V. All rights reserved.

Psychophysiology of Aggression, Psychopathy, and Conduct Problems: A Meta-Analysis

ERIC Educational Resources Information Center

Lorber, Michael F.

2004-01-01

A meta-analysis of 95 studies was conducted to investigate the relations of heart rate (HR) and electrodermal activity (EDA) with aggression, psychopathy, and conduct problems. Analyses revealed a complex constellation of interactive effects, with a failure in some cases of autonomic patterns to generalize across antisocial spectrum behavior…

Purification and characterization of a trehalase-invertase enzyme with dual activity from Candida utilis.

PubMed

Lahiri, Sagar; Basu, Arghya; Sengupta, Shinjinee; Banerjee, Shakri; Dutta, Trina; Soren, Dhananjay; Chattopadhyay, Krishnananda; Ghosh, Anil K

2012-06-15

Trehalose and sucrose, two important anti-stress non-reducing natural disaccharides, are catabolized by two enzymes, namely trehalase and invertase respectively. In this study, a 175 kDa enzyme protein active against both substrates was purified from wild type Candida utilis and characterized in detail. Substrate specificity assay and activity staining revealed the enzyme to be specific for both sucrose and trehalose. The ratio between trehalase and invertase activity was found to be constant at 1:3.5 throughout the entire study. Almost 40-fold purification and 30% yield for both activities were achieved at the final step of purification. The presence of common enzyme inhibitors, thermal and pH stress had analogous effects on its trehalase and invertase activity. Km values for two activities were similar while Vmax and Kcat also differed by a factor of 3.5. Competition plot for both substrates revealed the two activities to be occurring at the single active site. N-terminal sequencing and MALDI-TOF data analysis revealed higher similarity of the purified protein to previously known neutral trehalases. While earlier workers mentioned independent purification of neutral trehalase or invertase from different sources, the present study reports the purification of a single protein showing dual activity. Copyright © 2012 Elsevier Inc. All rights reserved.

Anticariogenic activity and phytochemical studies of crude extract from some Indian plant leaves

PubMed Central

Barad, Mahesh K.; Ishnava, Kalpesh B.; Chauhan, Jenabhai B.

2014-01-01

Aim: The aim was to screen the selected Indian plants for their antibacterial efficacy against four cariogenic bacteria Lactobacillus acidophilus (LA)(Microbial Type Culture Collection [MTCC]-*447), Lactobacillus casei (LC) (MTCC-1423), Streptococcus mutans (SMU) (MTCC-890) and Staphylococcus aureus (MTCC-96). To identify and characterize active principle present in these plants for the treatment of dental caries. Materials and Methods: The dried plant leaves materials are extracted by cold extraction using hexane, ethyl acetate, methanol, and distilled water. The solvents were evaporated, and the dried masses were suspended in dimethyl sulfoxide and used for anticariogenic activity by agar well diffusion method. Minimum inhibitory concentration (MIC) was evaluated by two-fold serial broth dilution method. Preliminary phytochemical analysis of effective extract was carried out by thin-layer chromatography (TLC) and bioautography. Results: Ethyl acetate and hexane extract of Eucalyptus globules was found most effective against L. acidophilus with MIC value 31 μg/ml and 62 μg/ml, respectively. Ethyl acetate extracts of Acacia nilotica and methanolic extract of E. globules also exhibited antibacterial activity against SMU and L. casei with MIC value of 50 μg/ml. Qualitative analysis of E. globules revealed the presence of alkaloids, terpenoids, phenolic compounds, and cardiac glycosides. The active principle responsible for the anticariogenic activity from E. globules were separated by TLC and subjected to bioautography using SMU, LA and LC. Conclusion: Anticariogenic activity and preliminary phytochemical analysis revealed that E. globule have potential to treat dental caries. PMID:26401353

A theoretical study on the characteristics of the intermolecular interactions in the active site of human androsterone sulphotransferase: DFT calculations of NQR and NMR parameters and QTAIM analysis.

PubMed

Astani, Elahe K; Heshmati, Emran; Chen, Chun-Jung; Hadipour, Nasser L

2016-07-01

A theoretical study at the level of density functional theory (DFT) was performed to characterize noncovalent intermolecular interactions, especially hydrogen bond interactions, in the active site of enzyme human androsterone sulphotransferase (SULT2A1/ADT). Geometry optimization, interaction energy, (2)H, (14)N, and (17)O electric field gradient (EFG) tensors, (1)H, (13)C, (17)O, and (15)N chemical shielding (CS) tensors, Natural Bonding Orbital (NBO) analysis, and quantum theory of atoms in molecules (QTAIM) analysis of this active site were investigated. It was found that androsterone (ADT) is able to form hydrogen bonds with residues Ser80, Ile82, and His99 of the active site. The interaction energy calculations and NBO analysis revealed that the ADT molecule forms the strongest hydrogen bond with Ser80. Results revealed that ADT interacts with the other residues through electrostatic and Van der Waals interactions. Results showed that these hydrogen bonds influence on the calculated (2)H, (14)N, and (17)O quadrupole coupling constants (QCCs), as well as (1)H, (13)C, (17)O, and (15)N CS tensors. The magnitude of the QCC and CS changes at each nucleus depends directly on its amount of contribution to the hydrogen bond interaction. Copyright © 2016 Elsevier Inc. All rights reserved.

Comparative analysis of fungal genomes reveals different plant cell wall degrading capacity in fungi

PubMed Central

2013-01-01

Background Fungi produce a variety of carbohydrate activity enzymes (CAZymes) for the degradation of plant polysaccharide materials to facilitate infection and/or gain nutrition. Identifying and comparing CAZymes from fungi with different nutritional modes or infection mechanisms may provide information for better understanding of their life styles and infection models. To date, over hundreds of fungal genomes are publicly available. However, a systematic comparative analysis of fungal CAZymes across the entire fungal kingdom has not been reported. Results In this study, we systemically identified glycoside hydrolases (GHs), polysaccharide lyases (PLs), carbohydrate esterases (CEs), and glycosyltransferases (GTs) as well as carbohydrate-binding modules (CBMs) in the predicted proteomes of 103 representative fungi from Ascomycota, Basidiomycota, Chytridiomycota, and Zygomycota. Comparative analysis of these CAZymes that play major roles in plant polysaccharide degradation revealed that fungi exhibit tremendous diversity in the number and variety of CAZymes. Among them, some families of GHs and CEs are the most prevalent CAZymes that are distributed in all of the fungi analyzed. Importantly, cellulases of some GH families are present in fungi that are not known to have cellulose-degrading ability. In addition, our results also showed that in general, plant pathogenic fungi have the highest number of CAZymes. Biotrophic fungi tend to have fewer CAZymes than necrotrophic and hemibiotrophic fungi. Pathogens of dicots often contain more pectinases than fungi infecting monocots. Interestingly, besides yeasts, many saprophytic fungi that are highly active in degrading plant biomass contain fewer CAZymes than plant pathogenic fungi. Furthermore, analysis of the gene expression profile of the wheat scab fungus Fusarium graminearum revealed that most of the CAZyme genes related to cell wall degradation were up-regulated during plant infection. Phylogenetic analysis also revealed a complex history of lineage-specific expansions and attritions for the PL1 family. Conclusions Our study provides insights into the variety and expansion of fungal CAZyme classes and revealed the relationship of CAZyme size and diversity with their nutritional strategy and host specificity. PMID:23617724

Caffeine - rich infusion from Cola nitida (kola nut) inhibits major carbohydrate catabolic enzymes; abates redox imbalance; and modulates oxidative dysregulated metabolic pathways and metabolites in Fe2+-induced hepatic toxicity.

PubMed

Erukainure, Ochuko L; Oyebode, Olajumoke A; Sokhela, Mxolisi K; Koorbanally, Neil A; Islam, Md Shahidul

2017-12-01

The antioxidative and antidiabetic effects and toxicity of caffeine-rich infusion of Cola nitida were investigated using in vitro, ex vivo and in silico models. C. nitida was infused in boiling water and allowed to cool before concentrating at <50°C. HPLC analysis of the infusion revealed a caffeine content of 80.08%. The infusion showed potent in vitro antioxidant activity by significantly (p<0.05) scavenging 2,2'-diphenyl-1-picrylhydrazyl (DPPH). It significantly (p<0.05) inhibited α-glucosidase and α-amylase activities. Treatment of Fe 2+ induced oxidative hepatic tissues with the infusion led to increase Superoxide Dismutase (SOD) and catalase activities, and glutathione (GSH) level as well as decreased malondialdehyde (MDA) level. FTIR spectroscopy of hepatic metabolite revealed restoration of oxidative-induced depleted functional groups by the infusion. LC-MS analysis of the metabolite also revealed restoration of most depleted metabolites with concomitant generation of 4-O-Methylgallic, (-)-Epicatechin sulfate, L-Arginine, L-tyrosine, Citric acid and Decanoic acid in infusion-treated tissues. Pathway analysis of the identified metabolites revealed the presence of 21 metabolic pathways involved in normal hepatic tissues, 12 in oxidative injured tissues and 17 in the treated tissues. Treatment with the infusion restored 4 metabolic pathways common to the normal tissue and further activated 4 additional pathways. Prediction of oral toxicity of caffeine showed it to belong to class 3, with a LD 50 of 127mg/kg. Its toxicity target was predicted as Adenosine Receptor A2a. It was also predicted to be an inhibitor of CYP1A2. These results suggest the antioxidative and antidiabetic properties of C. nitida infusion, with caffeine as the major constituent. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Contextualizing Teacher Professionalism: Findings from a Cross-Case Analysis of Union Active Teachers

ERIC Educational Resources Information Center

Osmond-Johnson, Pamela

2016-01-01

This paper draws on data collected as part of a study of the discourses of teacher professionalism amongst union active teachers in the Canadian provinces of Alberta and Ontario. Interviews revealed a triad of influences on the professionalism discourses of participants: engagement in teacher associations, the larger policy environment, and…

The Analysis of Extracurricular Activities and Their Relationship to Youth Violence

ERIC Educational Resources Information Center

Linville, Deanna C.; Huebner, Angela J.

2005-01-01

The purpose of this study was to examine how extracurricular activities relate to rural youth violence. Gender differences were examined across all of the study variables. Self-report data were collected from 235 teenagers from a rural, ethnically diverse, Virginia community. Correlations revealed a significant inverse relationship between church…

Mexican American Women's Activism at Indiana University in the 1990s

ERIC Educational Resources Information Center

Hernandez, Ebelia

2013-01-01

This article offers a historical analysis of documents and narratives from Mexican American women that reflect the tumultuous 1990s at Indiana University. Their recollections reveal how they became activists, the racist incidents that compelled them into activism, and the racial tensions and backlash towards identity politics felt by students of…

Monitoring Social Media: Students Satisfaction with University Administration Activities

ERIC Educational Resources Information Center

Koshkin, Andrey Petrovich; Rassolov, Ilya Mihajlovich; Novikov, Andrey Vadimovich

2017-01-01

The paper presents an original method of identifying satisfaction of students with the activities of their university administration based on studying the content of comments on the social networks. The analysis of student opinions revealed areas of concern and priority areas in the work of the university administration. The paper characterizes…

Analysis of the Heat Shock Response in Mouse Liver Reveals Transcriptional Dependence on the Nuclear Receptor Peroxisome Proliferator-Activated Receptor alpha (PPARα)

EPA Science Inventory

BACKGROUND: The nuclear receptor peroxisome proliferator-activated receptor alpha (PPARalpha) regulates responses to chemical or physical stress in part by altering expression of genes involved in proteome maintenance. Many of these genes are also transcriptionally regulated by h...

Protease-activated receptor-2 stimulates intestinal epithelial chloride transport through activation of PLC and selective PKC isoforms.

PubMed

van der Merwe, Jacques Q; Moreau, France; MacNaughton, Wallace K

2009-06-01

Serine proteases play important physiological roles through their activity at G protein-coupled protease-activated receptors (PARs). We examined the roles that specific phospholipase (PL) C and protein kinase (PK) C (PKC) isoforms play in the regulation of PAR(2)-stimulated chloride secretion in intestinal epithelial cells. Confluent SCBN epithelial monolayers were grown on Snapwell supports and mounted in modified Ussing chambers. Short-circuit current (I(sc)) responses to basolateral application of the selective PAR(2) activating peptide, SLIGRL-NH(2), were monitored as a measure of net electrogenic ion transport caused by PAR(2) activation. SLIGRL-NH(2) induced a transient I(sc) response that was significantly reduced by inhibitors of PLC (U73122), phosphoinositol-PLC (ET-18), phosphatidylcholine-PLC (D609), and phosphatidylinositol 3-kinase (PI3K; LY294002). Immunoblot analysis revealed the phosphorylation of both PLCbeta and PLCgamma following PAR(2) activation. Pretreatment of the cells with inhibitors of PKC (GF 109203X), PKCalpha/betaI (Gö6976), and PKCdelta (rottlerin), but not PKCzeta (selective pseudosubstrate inhibitor), also attenuated this response. Cellular fractionation and immunoblot analysis, as well as confocal immunocytochemistry, revealed increases of PKCbetaI, PKCdelta, and PKCepsilon, but not PKCalpha or PKCzeta, in membrane fractions following PAR(2) activation. Pretreatment of the cells with U73122, ET-18, or D609 inhibited PKC activation. Inhibition of PI3K activity only prevented PKCdelta translocation. Immunoblots revealed that PAR(2) activation induced phosphorylation of both cRaf and ERK1/2 via PKCdelta. Inhibition of PKCbetaI and PI3K had only a partial effect on this response. We conclude that basolateral PAR(2)-induced chloride secretion involves activation of PKCbetaI and PKCdelta via a PLC-dependent mechanism resulting in the stimulation of cRaf and ERK1/2 signaling.

Contextual and perceptual brain processes underlying moral cognition: a quantitative meta-analysis of moral reasoning and moral emotions.

PubMed

Sevinc, Gunes; Spreng, R Nathan

2014-01-01

Human morality has been investigated using a variety of tasks ranging from judgments of hypothetical dilemmas to viewing morally salient stimuli. These experiments have provided insight into neural correlates of moral judgments and emotions, yet these approaches reveal important differences in moral cognition. Moral reasoning tasks require active deliberation while moral emotion tasks involve the perception of stimuli with moral implications. We examined convergent and divergent brain activity associated with these experimental paradigms taking a quantitative meta-analytic approach. A systematic search of the literature yielded 40 studies. Studies involving explicit decisions in a moral situation were categorized as active (n = 22); studies evoking moral emotions were categorized as passive (n = 18). We conducted a coordinate-based meta-analysis using the Activation Likelihood Estimation to determine reliable patterns of brain activity. Results revealed a convergent pattern of reliable brain activity for both task categories in regions of the default network, consistent with the social and contextual information processes supported by this brain network. Active tasks revealed more reliable activity in the temporoparietal junction, angular gyrus and temporal pole. Active tasks demand deliberative reasoning and may disproportionately involve the retrieval of social knowledge from memory, mental state attribution, and construction of the context through associative processes. In contrast, passive tasks reliably engaged regions associated with visual and emotional information processing, including lingual gyrus and the amygdala. A laterality effect was observed in dorsomedial prefrontal cortex, with active tasks engaging the left, and passive tasks engaging the right. While overlapping activity patterns suggest a shared neural network for both tasks, differential activity suggests that processing of moral input is affected by task demands. The results provide novel insight into distinct features of moral cognition, including the generation of moral context through associative processes and the perceptual detection of moral salience.

Contextual and Perceptual Brain Processes Underlying Moral Cognition: A Quantitative Meta-Analysis of Moral Reasoning and Moral Emotions

PubMed Central

Sevinc, Gunes; Spreng, R. Nathan

2014-01-01

Background and Objectives Human morality has been investigated using a variety of tasks ranging from judgments of hypothetical dilemmas to viewing morally salient stimuli. These experiments have provided insight into neural correlates of moral judgments and emotions, yet these approaches reveal important differences in moral cognition. Moral reasoning tasks require active deliberation while moral emotion tasks involve the perception of stimuli with moral implications. We examined convergent and divergent brain activity associated with these experimental paradigms taking a quantitative meta-analytic approach. Data Source A systematic search of the literature yielded 40 studies. Studies involving explicit decisions in a moral situation were categorized as active (n = 22); studies evoking moral emotions were categorized as passive (n = 18). We conducted a coordinate-based meta-analysis using the Activation Likelihood Estimation to determine reliable patterns of brain activity. Results & Conclusions Results revealed a convergent pattern of reliable brain activity for both task categories in regions of the default network, consistent with the social and contextual information processes supported by this brain network. Active tasks revealed more reliable activity in the temporoparietal junction, angular gyrus and temporal pole. Active tasks demand deliberative reasoning and may disproportionately involve the retrieval of social knowledge from memory, mental state attribution, and construction of the context through associative processes. In contrast, passive tasks reliably engaged regions associated with visual and emotional information processing, including lingual gyrus and the amygdala. A laterality effect was observed in dorsomedial prefrontal cortex, with active tasks engaging the left, and passive tasks engaging the right. While overlapping activity patterns suggest a shared neural network for both tasks, differential activity suggests that processing of moral input is affected by task demands. The results provide novel insight into distinct features of moral cognition, including the generation of moral context through associative processes and the perceptual detection of moral salience. PMID:24503959

Metabolic profile and biological activities of Lavandula pedunculata subsp. lusitanica (Chaytor) Franco: studies on the essential oil and polar extracts.

PubMed

Costa, Patrícia; Gonçalves, Sandra; Valentão, Patrícia; Andrade, Paula B; Almeida, Carlos; Nogueira, José M F; Romano, Anabela

2013-12-01

We investigated the metabolic profile and biological activities of the essential oil and polar extracts of Lavandula pedunculata subsp. lusitanica (Chaytor) Franco collected in south Portugal. Gas chromatography-mass spectrometry (GC-MS) analysis revealed that oxygen-containing monoterpenes was the principal group of compounds identified in the essential oil. Camphor (40.6%) and fenchone (38.0%) were found as the major constituents. High-performance liquid chromatography with diode array detection (HPLC-DAD) analysis allowed the identification of hydroxycinnamic acids (3-O-caffeoylquinic, 4-O-caffeoylquinic, 5-O-caffeoylquinic and rosmarinic acids) and flavones (luteolin and apigenin) in the polar extracts, with rosmarinic acid being the main compound in most of them. The bioactive compounds from L. pedunculata polar extracts were the most efficient free-radical scavengers, Fe(2+) chelators and inhibitors of malondialdehyde production, while the essential oil was the most active against acetylcholinesterase. Our results reveal that the subspecies of L. pedunculata studied is a potential source of active metabolites with a positive effect on human health. Copyright © 2013 Elsevier Ltd. All rights reserved.

Genome mining-directed activation of a silent angucycline biosynthetic gene cluster in Streptomyces chattanoogensis.

PubMed

Zhou, Zhenxing; Xu, Qingqing; Bu, Qingting; Guo, Yuanyang; Liu, Shuiping; Liu, Yu; Du, Yiling; Li, Yongquan

2015-02-09

Genomic sequencing of actinomycetes has revealed the presence of numerous gene clusters seemingly capable of natural product biosynthesis, yet most clusters are cryptic under laboratory conditions. Bioinformatics analysis of the completely sequenced genome of Streptomyces chattanoogensis L10 (CGMCC 2644) revealed a silent angucycline biosynthetic gene cluster. The overexpression of a pathway-specific activator gene under the constitutive ermE* promoter successfully triggered the expression of the angucycline biosynthetic genes. Two novel members of the angucycline antibiotic family, chattamycins A and B, were further isolated and elucidated. Biological activity assays demonstrated that chattamycin B possesses good antitumor activities against human cancer cell lines and moderate antibacterial activities. The results presented here provide a feasible method to activate silent angucycline biosynthetic gene clusters to discover potential new drug leads. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Structural analysis of proanthocyanidins isolated from fruit stone of Chinese hawthorn with potent antityrosinase and antioxidant activity.

PubMed

Chai, Wei-Ming; Chen, Chih-Min; Gao, Yu-Sen; Feng, Hui-Ling; Ding, Yu-Mei; Shi, Yan; Zhou, Han-Tao; Chen, Qing-Xi

2014-01-08

Proanthocyanidins were isolated from fruit stone of Chinese hawthorn (Crataegus pinnatifida Bge. var. major N.E.Br.). Their structures were analyzed and elucidated by methods of matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) and high performance liquid chromatography electrospray ionization mass spectrometry (HPLC-ESI-MS). The results demonstrated that these compounds are complicated mixtures of homo- and heteropolymers consisting of procyanidin/procyanidin gallate and prodelphinidin. They possessed structural heterogeneity in monomer units, polymer length, and interflavan linkage (A-type and B-type). Their antityrosinase and antioxidant activity were then investigated. The results revealed that they can inhibit tyrosinase activities, including the monophenolase activity and the diphenolase activity. In addition, proanthocyanidins possessed potent antioxidant activity. Our studies revealed that proanthocyanidins isolated from fruit stone of Chinese hawthorn may be applied in food, agriculture, pharmaceutical, and cosmetic industries.

Cytoprotective effect of seaweeds with high antioxidant activity from the Peniche coast (Portugal).

PubMed

Pinteus, Susete; Silva, Joana; Alves, Celso; Horta, André; Fino, Nádia; Rodrigues, Ana Inês; Mendes, Susana; Pedrosa, Rui

2017-03-01

Screening of antioxidant potential of dichloromethane and methanolic extracts of twenty-seven seaweeds from the Peniche coast was performed by: total phenolic contents (TPC), 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity and oxygen radical absorbance capacity (ORAC). Seaweeds revealing the highest antioxidant activity were screened for cytoprotective potential in MCF-7 cells, including the mitochondrial membrane potential analysis and the caspase-9 activity. High correlation was found between TPC of seaweed extracts and their scavenging capacity on DPPH and peroxyl radicals. The highest antioxidant activity was displayed by the methanolic fraction of brown seaweeds belonging to Fucales, however Ulva compressa presented the highest cytoprotective effect by blunting the apoptosis process. These results suggest that high antioxidant activity may not be directly related with high cytoprotective potential. Thus, seaweeds reveal to be a promising source of compounds with potential against oxidative stress. Copyright © 2016 Elsevier Ltd. All rights reserved.

Genome-Wide Survey and Expression Profiling of CCCH-Zinc Finger Family Reveals a Functional Module in Macrophage Activation

PubMed Central

Liang, Jian; Song, Wenjun; Tromp, Gail; Kolattukudy, Pappachan E.; Fu, Mingui

2008-01-01

Previously, we have identified a novel CCCH zinc finger protein family as negative regulators of macrophage activation. To gain an overall insight into the entire CCCH zinc finger gene family and to evaluate their potential role in macrophage activation, here we performed a genome-wide survey of CCCH zinc finger genes in mouse and human. Totally 58 CCCH zinc finger genes in mouse and 55 in human were identified and most of them have not been reported previously. Phylogenetic analysis revealed that the mouse CCCH family was divided into 6 groups. Meanwhile, we employed quantitative real-time PCR to profile their tissue expression patterns in adult mice. Clustering analysis showed that most of CCCH genes were broadly expressed in all of tissues examined with various levels. Interestingly, several CCCH genes Mbnl3, Zfp36l2, Zfp36, Zc3h12a, Zc3h12d, Zc3h7a and Leng9 were enriched in macrophage-related organs such as thymus, spleen, lung, intestine and adipose. Consistently, a comprehensive assessment of changes in expression of the 58 members of the mouse CCCH family during macrophage activation also revealed that these CCCH zinc finger genes were associated with the activation of bone marrow-derived macrophages by lipopolysaccharide. Taken together, this study not only identified a functional module of CCCH zinc finger genes in the regulation of macrophage activation but also provided the framework for future studies to dissect the function of this emerging gene family. PMID:18682727

Bioinspired green synthesis of copper oxide nanoparticles from Syzygium alternifolium (Wt.) Walp: characterization and evaluation of its synergistic antimicrobial and anticancer activity

NASA Astrophysics Data System (ADS)

Yugandhar, Pulicherla; Vasavi, Thirumalanadhuni; Uma Maheswari Devi, Palempalli; Savithramma, Nataru

2017-10-01

In recent times, nanoparticles are attributed to green nanotechnology methods to know the synergistic biological activities. To accomplish this phenomenon, present study was aimed to synthesize copper oxide nanoparticles (CuO NPs) by using Syzygium alternifolium stem bark, characterized those NPs using expository tools and to elucidate high prioritized antimicrobial and anticancer activities. Synthesized particles exhibited a color change pattern upon synthesis and affirmed its respective broad peak at 285 nm which was analyzed through UV-vis spectroscopy. FT-IR study confirmed that phenols and primary amines were mainly involved in capping and stabilization of nanoparticles. DLS and Zeta potential studies revealed narrow size of particles with greater stability. XRD studies revealed the crystallographic nature of particles with 17.2 nm average size. Microscopic analysis by using TEM revealed that particle size range from 5-13 nm and most of them were spherical in shape, non-agglomerated and poly-dispersed in condition. Antimicrobial studies of particles showed highest inhibitory activity against E. coli and T. harzianum among bacterial and fungal strains, respectively. The scope of this study is extended by examining anticancer activity of CuO NPs. This study exhibited potential anticancer activity towards MDA-MB-231 human breast cancer lines. Overall, these examinations relate that the S. alternifolium is described as efficient well-being plant and probabilistically for the design and synthesis of nanoparticles for human health. This study paves a way to better understand antimicrobial and anticancer therapeutic drug potentials of nanoparticles to design and analysis of pharmaceuticals by in vivo and in vitro approaches.

Variability in memory performance in aged healthy individuals: an fMRI study.

PubMed

Grön, Georg; Bittner, Daniel; Schmitz, Bernd; Wunderlich, Arthur P; Tomczak, Reinhard; Riepe, Matthias W

2003-01-01

Episodic memory performance varies in older subjects but underlying biological correlates remain as yet ambiguous. We investigated episodic memory in healthy older individuals (n=24; mean age: 64.4+/-6.7 years) without subjective memory complaints or objective cognitive impairment. Episodic memory was assessed with repetitive learning and recall of abstract geometric patterns during fMRI. Group analysis of brain activity during initial learning and maximum recall revealed hippocampal activation. Correlation analysis of brain activation and task performance demonstrated significant hippocampal activity during initial learning and maximum recall in a success-dependent manner. Neither age nor gray matter densities correlated with hippocampal activation. Functional imaging of episodic memory thus permits to detect objectively variability in hippocampal recruitment in healthy aged individuals without subjective memory complaints. Correlation analysis of brain activation and performance during an episodic memory task may be used to determine and follow-up hippocampal malfunction in a very sensitive manner.

A combined planning and self-efficacy intervention to promote physical activity: a multiple mediation analysis.

PubMed

Koring, Milena; Richert, Jana; Parschau, Linda; Ernsting, Anna; Lippke, Sonia; Schwarzer, Ralf

2012-01-01

Many individuals are motivated to improve their physical activity levels, but often fail to act upon their intention. Interventions fostering volitional strategies, such as action planning, coping planning, and self-efficacy beliefs, can help to translate intentions into behavior. This study examines the effectiveness and the mechanisms of a combined planning and self-efficacy intervention to promote physical activity among motivated individuals. Participants (N = 883) were randomly assigned to the intervention or to a waiting-list control condition. Multivariate analysis of variance revealed that the intervention resulted in significantly more physical activity, higher levels of action planning, coping planning, and volitional self-efficacy beliefs (p < 0.01). In addition, multiple mediation analysis showed that action planning, coping planning, and volitional self-efficacy mediate between the intervention and physical activity. The study shows that the intervention successfully fostered physical activity and unfolds the underlying self-regulatory mechanisms of the intervention's effectiveness.

Non-extensivity and complexity in the earthquake activity at the West Corinth rift (Greece)

NASA Astrophysics Data System (ADS)

Michas, Georgios; Vallianatos, Filippos; Sammonds, Peter

2013-04-01

Earthquakes exhibit complex phenomenology that is revealed from the fractal structure in space, time and magnitude. For that reason other tools rather than the simple Poissonian statistics seem more appropriate to describe the statistical properties of the phenomenon. Here we use Non-Extensive Statistical Physics [NESP] to investigate the inter-event time distribution of the earthquake activity at the west Corinth rift (central Greece). This area is one of the most seismotectonically active areas in Europe, with an important continental N-S extension and high seismicity rates. NESP concept refers to the non-additive Tsallis entropy Sq that includes Boltzmann-Gibbs entropy as a particular case. This concept has been successfully used for the analysis of a variety of complex dynamic systems including earthquakes, where fractality and long-range interactions are important. The analysis indicates that the cumulative inter-event time distribution can be successfully described with NESP, implying the complexity that characterizes the temporal occurrences of earthquakes. Further on, we use the Tsallis entropy (Sq) and the Fischer Information Measure (FIM) to investigate the complexity that characterizes the inter-event time distribution through different time windows along the evolution of the seismic activity at the West Corinth rift. The results of this analysis reveal a different level of organization and clusterization of the seismic activity in time. Acknowledgments. GM wish to acknowledge the partial support of the Greek State Scholarships Foundation (IKY).

Comparative Proteomics Analysis Reveals L-Arginine Activates Ethanol Degradation Pathways in HepG2 Cells.

PubMed

Yan, Guokai; Lestari, Retno; Long, Baisheng; Fan, Qiwen; Wang, Zhichang; Guo, Xiaozhen; Yu, Jie; Hu, Jun; Yang, Xingya; Chen, Changqing; Liu, Lu; Li, Xiuzhi; Purnomoadi, Agung; Achmadi, Joelal; Yan, Xianghua

2016-03-17

L-Arginine (Arg) is a versatile amino acid that plays crucial roles in a wide range of physiological and pathological processes. In this study, to investigate the alteration induced by Arg supplementation in proteome scale, isobaric tags for relative and absolute quantification (iTRAQ) based proteomic approach was employed to comparatively characterize the differentially expressed proteins between Arg deprivation (Ctrl) and Arg supplementation (+Arg) treated human liver hepatocellular carcinoma (HepG2) cells. A total of 21 proteins were identified as differentially expressed proteins and these 21 proteins were all up-regulated by Arg supplementation. Six amino acid metabolism-related proteins, mostly metabolic enzymes, showed differential expressions. Intriguingly, Ingenuity Pathway Analysis (IPA) based pathway analysis suggested that the three ethanol degradation pathways were significantly altered between Ctrl and +Arg. Western blotting and enzymatic activity assays validated that the key enzymes ADH1C, ALDH1A1, and ALDH2, which are mainly involved in ethanol degradation pathways, were highly differentially expressed, and activated between Ctrl and +Arg in HepG2 cells. Furthermore, 10 mM Arg significantly attenuated the cytotoxicity induced by 100 mM ethanol treatment (P < 0.0001). This study is the first time to reveal that Arg activates ethanol degradation pathways in HepG2 cells.

Analysis of the Mycoplasma bovis lactate dehydrogenase reveals typical enzymatic activity despite the presence of an atypical catalytic site motif.

PubMed

Masukagami, Yumiko; Tivendale, Kelly Anne; Browning, Glenn Francis; Sansom, Fiona Margaret

2018-02-01

The lactate dehydrogenase (LDH) of Mycoplasma genitalium has been predicted to also act as a malate dehydrogenase (MDH), but there has been no experimental validation of this hypothesized dual function for any mollicute. Our analysis of the metabolite profile of Mycoplasma bovis using gas chromatography/mass spectrometry (GC/MS) and liquid chromatography/mass spectrometry (LC/MS) detected malate, suggesting that there may be MDH activity in M. bovis. To investigate whether the putative l-LDH enzyme of M. bovis has a dual function (MDH and LDH), we performed bioinformatic and functional biochemical analyses. Although the amino acid sequence and predicted structural analysis of M. bovisl-LDH revealed unusual residues within the catalytic site, suggesting that it may have the flexibility to possess a dual function, our biochemical studies using recombinant M. bovis -LDH did not detect any MDH activity. However, we did show that the enzyme has typical LDH activity that could be inhibited by both MDH substrates oxaloacetate (OAA) and malate, suggesting that these substrates may be able to bind to M. bovis LDH. Inhibition of the conversion of pyruvate to lactate by OAA may be one method the mycoplasma cell uses to reduce the potential for accumulation of intracellular lactate.

Screening of analgesic activity of Tunisian Urtica dioica and analysis of its major bioactive compounds by GCMS.

PubMed

Dhouibi, Raouia; Moalla, Dorsaf; Ksouda, Kamilia; Ben Salem, Maryem; Hammami, Serria; Sahnoun, Zouheir; Zeghal, Khaled Mounir; Affes, Hanen

2017-11-20

The present study was aimed to evaluate the analgesic properties of Urtica dioica (UD) and to profile phytochemicals by gas chromatography-mass spectrometry (GC-MS). The ethanolic extracts were prepared by maceration method and extraction using rotary evaporator. The analgesic activity was analysed by hot plate method, formalin test, acetic acid-induced writhing test and the tail-flick test with different doses of the ethanolic extract. In all tests, the leaf's ethanolic extract exhibited significant analgesic activity (p < .001) at a dose of 400 mg/kg. Even with a low dose, we noticed an analgesic activity with many tests. The GC-MS analysis of the ethanol extract of leaf revealed many compounds; 2-methyltetradecane dodecane, 2,6,11-trimethyl-; 2,6,11-trimethyldodecane, and trimethylhexane which are pharmaceutically the most important. These findings justify that UD can be a valuable natural analgesic source which seemed to provide potential phototherapeutics against various ailments. The analysis of ethanolic extract of UD by GCMS revealed the presence of several compounds including polyphenols, flavonoids, triterpenes which can explain the analgesic effect of UD and its mechanism of action. Hence, UD could be another therapeutic alternative for relieving pain and for minimising the use of drugs that have long-term secondary effects.

Genetic Characterization and Physiological Role of Endopeptidase O from Lactobacillus helveticus CNRZ32

PubMed Central

Chen, Yo-Shen; Steele, James L.

1998-01-01

A previously identified insert expressing an endopeptidase from a Lactobacillus helveticus CNRZ32 genomic library was characterized. Nucleotide sequence analysis revealed an open reading frame of 1,941 bp encoding a putative protein of 71.2 kDa which contained a zinc-protease motif. Protein homology searches revealed that this enzyme has 40% similarity with endopeptidase O (PepO) from Lactococcus lactis P8-2-47. Northern hybridization revealed that pepO is monocistronic and is expressed throughout the growth phase. CNRZ32 derivatives lacking PepO activity were constructed via gene replacement. Enzyme assays revealed that the PepO mutant had significantly reduced endopeptidase activity when compared to CNRZ32 with two of the three substrates examined. Growth studies indicated that PepO has no detectable effect on growth rate or acid production by Lactobacillus helveticus CNRZ32 in amino acid defined or skim milk medium. PMID:9726890

Response of Ca2+-ATPase to clinorotaion of pea seedlings. O. M. Nedukha and E. L. Kordyum

NASA Astrophysics Data System (ADS)

Nedukha, Olena

2016-07-01

The present study was aimed to reveal of response of Ca2+-ATPase activity of cortex cells in distal elongation zone of Pisum sativum root to slow clinorotation. Pea seedlings were grown on a horizontal clinostat (2 rpm) and in the stationary control for 6 days. The electron-cytochemical method was used to examine the effects of imitated microgravity on the distribution of Ca2+-ATPase in outer layers of root cortex. The quantitative analysis of the density of cytochemical reaction products was measured using the Image J program. Electron microscopy showed the presence of electron-dense lead phosphate precipitated grains, the enzymatic activity reaction products on the plasma membrane, membranes of vesicular structures, endoplasmic reticulum (ER) and on organelles envelope in both of samples of the stationary control and clinorotated seedlings. We revealed the sensitivity of Ca2+-ATPase to clinorotation. The quantitative analysis of the area and density of enzymatic activity reaction products revealed that clinorotation led to the decrease of 3.4 times the density of reaction products on the plasma membrane and the increase of reaction products density on endomembranes and organelles membranes, in particular: in 2.2 times on mitochondria membranes; in 1.3 times - on membranes of ER; in 2.5 times - on tonoplast; by an order of magnitude greater - on contacting membranes of organelles with plasma membrane in comparison with such in cells of control samples. The data analysis can indicate an intensification of calcium pump on endomembranes, on envelopes of cytoplasmic organelles and nucleus. The obtained data suggest that the redistribution of Ca2+-ATPase activity in cells can be mediated by the activation of certain isoforms of enzyme or/and by an activation of Ca2+/H+ antiporter in plasma membrane that helps to maintain optimal calcium balance in plant cells under imitated microgravity.

Computer-assisted three-dimensional reconstructions of ( sup 14 C)-2-deoxy-D-glucose metabolism in cat lumbosacral spinal cord following cutaneous stimulation of the hindfoot

DOE Office of Scientific and Technical Information (OSTI.GOV)

Crockett, D.P.; Smith, W.K.; Proshansky, E.

1989-10-08

We report on computer-assisted three-dimensional reconstruction of spinal cord activity associated with stimulation of the plantar cushion (PC) as revealed by (14C)-2-deoxy-D-glucose (2-DG) serial autoradiographs. Moderate PC stimulation in cats elicits a reflex phasic plantar flexion of the toes. Four cats were chronically spinalized at about T6 under barbiturate anesthesia. Four to 11 days later, the cats were injected (i.v.) with 2-DG (100 microCi/kg) and the PC was electrically stimulated with needle electrodes at 2-5 times threshold for eliciting a reflex. Following stimulation, the spinal cord was processed for autoradiography. Subsequently, autoradiographs, representing approximately 8-18 mm from spinal segments L6-S1,more » were digitized for computer analysis and 3-D reconstruction. Several strategies of analysis were employed: (1) Three-dimensional volume images were color-coded to represent different levels of functional activity. (2) On the reconstructed volumes, virtual sections were made in the horizontal, sagittal, and transverse planes to view regions of 2-DG activity. (3) In addition, we were able to sample different regions within the grey and white matter semi-quantitatively (i.e., pixel intensity) from section to section to reveal differences between ipsi- and contralateral activity, as well as possible variation between sections. These analyses revealed 2-DG activity associated with moderate PC stimulation, not only in the ipsilateral dorsal horn as we had previously demonstrated, but also in both the ipsilateral and contralateral ventral horns, as well as in the intermediate grey matter. The use of novel computer analysis techniques--combined with an unanesthetized preparation--enabled us to demonstrate that the increased metabolic activity in the lumbosacral spinal cord associated with PC stimulation was much more extensive than had heretofore been observed.« less

Possible influence of solar extreme events and related geomagnetic disturbances on human cardio-vascular state: Results of collaborative Bulgarian-Azerbaijani studies

NASA Astrophysics Data System (ADS)

Dimitrova, S.; Mustafa, F. R.; Stoilova, I.; Babayev, E. S.; Kazimov, E. A.

2009-02-01

This collaborative study is based on the analysis and comparison of results of coordinated experimental investigations conducted in Bulgaria and Azerbaijan for revealing a possible influence of solar activity changes and related geomagnetic activity variations on the human cardio-vascular state. Arterial blood pressure and heart rate of 86 healthy volunteers were measured on working days during a period of comparatively high solar and geomagnetic activity (2799 measurements in autumn 2001 and spring 2002) in Sofia. Daily experimental investigations of parameters of cardio-vascular health state were performed in Azerbaijan with a permanent group of examined persons. Heart rate and electrocardiograms were digitally registered (in total 1532 records) for seven functionally healthy persons on working days and Saturdays, in the Laboratory of Heliobiology at the Medical Center INAM in Baku, from 15.07.2006 to 13.11.2007. Obtained digital recordings were subjected to medical, statistical and spectral analyses. Special attention was paid to effects of solar extreme events, particularly those of November 2001 and December 2006. The statistical method of the analysis of variance (ANOVA) and post hoc analysis were applied to check the significance of the influence of geomagnetic activity on the cardio-vascular parameters under consideration. Results revealed statistically significant increments for the mean systolic and diastolic blood pressure values of the group with geomagnetic activity increase. Arterial blood pressure values started increasing two days prior to geomagnetic storms and kept their high values up to two days after the storms. Heart rate reaction was ambiguous and not significant for healthy persons examined (for both groups) under conditions with geomagnetic activity changes. It is concluded that heart rate for healthy persons at middle latitudes can be considered as a more stable physiological parameter which is not so sensitive to environmental changes while the dynamics of arterial blood pressure reveals a compensatory reaction of the human organism for adaptation.

Component analysis and free radicals scavenging activity of Cicer arietinum L. husk pectin.

PubMed

Urias-Orona, Vania; Huerta-Oros, Joselina; Carvajal-Millán, Elizabeth; Lizardi-Mendoza, Jaime; Rascón-Chu, Agustin; Gardea, Alfonso A

2010-10-11

A pectin (CAP) was extracted from the husk of Cicer arietinum L. Monosaccharide analysis of CAP revealed the dominance of galacturonic acid and smaller amounts of galactose, arabinose, rhamnose, glucose, xylose and mannose. Viscosimetric analysis showed that the intrinsic viscosity ([η]) and the molecular weight (MW) of CAP were 296 mL/g and 105 kDa, respectively. The degree of esterification (DE = 10%) was determined by FTIR spectroscopy. CAP exhibited a dose-dependent free radical scavenging activity, as shown by its DPPH radical inhibition. At 1.0 mg/mL CAP exhibited a scavenging rate of 29% on DPPH radicals. The evaluation of antioxidant activity suggested that CAP had good potential for DPPH radical scavenging activity and should be explored as a novel potential antioxidant.

[Construction of a professionnal juridiction in Adapted Physical Activity in the medical world].

PubMed

Perrin, Claire

2016-06-08

Analysis of interactions between professionals and patients with chronic diseases reveals a space invested by professional expertise in which APA teachers occupy their own distinctive position..

Crystal structure of Escherichia coli diaminopropionate ammonia-lyase reveals mechanism of enzyme activation and catalysis.

PubMed

Bisht, Shveta; Rajaram, Venkatesan; Bharath, Sakshibeedu R; Kalyani, Josyula Nitya; Khan, Farida; Rao, Appaji N; Savithri, Handanahal S; Murthy, Mathur R N

2012-06-08

Pyridoxal 5'-phosphate (PLP)-dependent enzymes utilize the unique chemistry of a pyridine ring to carry out diverse reactions involving amino acids. Diaminopropionate (DAP) ammonia-lyase (DAPAL) is a prokaryotic PLP-dependent enzyme that catalyzes the degradation of d- and l-forms of DAP to pyruvate and ammonia. Here, we report the first crystal structure of DAPAL from Escherichia coli (EcDAPAL) in tetragonal and monoclinic forms at 2.0 and 2.2 Å resolutions, respectively. Structures of EcDAPAL soaked with substrates were also determined. EcDAPAL has a typical fold type II PLP-dependent enzyme topology consisting of a large and a small domain with the active site at the interface of the two domains. The enzyme is a homodimer with a unique biological interface not observed earlier. Structure of the enzyme in the tetragonal form had PLP bound at the active site, whereas the monoclinic structure was in the apo-form. Analysis of the apo and holo structures revealed that the region around the active site undergoes transition from a disordered to ordered state and assumes a conformation suitable for catalysis only upon PLP binding. A novel disulfide was found to occur near a channel that is likely to regulate entry of ligands to the active site. EcDAPAL soaked with dl-DAP revealed density at the active site appropriate for the reaction intermediate aminoacrylate, which is consistent with the observation that EcDAPAL has low activity under crystallization conditions. Based on the analysis of the structure and results of site-directed mutagenesis, a two-base mechanism of catalysis involving Asp(120) and Lys(77) is suggested.

Congenital combined pituitary hormone deficiency attributable to a novel PROP1 mutation (467insT).

PubMed

Nose, Osamu; Tatsumi, Keita; Nakano, Yukiko; Amino, Nobuyuki

2006-04-01

Combined pituitary hormone deficiency (CPHD) is an anterior pituitary disorder, commonly resulting in growth retardation. PROP1 gene mutations appear to be frequently responsible for CPHD, particularly in Middle and Eastern Europe and the Americas, but few cases have been reported in Japan. Two sisters (aged 8.4 and 4.3 years at presentation) exhibited proportional short stature from about 2 years of age. Genetic analysis determined the nature and location of mutations. Pituitary size by magnetic resonance imaging (MRI) indicated only slight hypoplasia, while hormone analysis revealed deficiencies in secretion of growth hormone (GH), thyroid stimulating hormone, prolactin and gonadotropins; adrenocortinotropin secretion appeared adequate. Genetic analysis revealed a novel familial inherited PROP1 mutation. A unique insertion mutation was found in codon 156 (467insT) located in the transcription-activating region of the PROP1 gene. The resulting PROP1 protein (191 amino acids) would lack the transcription activation domain and consequently be non-functional. Gene analysis suggested that the siblings had inherited a unique autosomal recessive PROP1 gene mutation resulting in severe GH deficiency and subsequent growth retardation.

Macro-fingerprint analysis-through-separation of licorice based on FT-IR and 2DCOS-IR

NASA Astrophysics Data System (ADS)

Wang, Yang; Wang, Ping; Xu, Changhua; Yang, Yan; Li, Jin; Chen, Tao; Li, Zheng; Cui, Weili; Zhou, Qun; Sun, Suqin; Li, Huifen

2014-07-01

In this paper, a step-by-step analysis-through-separation method under the navigation of multi-step IR macro-fingerprint (FT-IR integrated with second derivative IR (SD-IR) and 2DCOS-IR) was developed for comprehensively characterizing the hierarchical chemical fingerprints of licorice from entirety to single active components. Subsequently, the chemical profile variation rules of three parts (flavonoids, saponins and saccharides) in the separation process were holistically revealed and the number of matching peaks and correlation coefficients with standards of pure compounds was increasing along the extracting directions. The findings were supported by UPLC results and a verification experiment of aqueous separation process. It has been demonstrated that the developed multi-step IR macro-fingerprint analysis-through-separation approach could be a rapid, effective and integrated method not only for objectively providing comprehensive chemical characterization of licorice and all its separated parts, but also for rapidly revealing the global enrichment trend of the active components in licorice separation process.

Structural and Functional Analysis of the Human HDAC4 Catalytic Domain Reveals a Regulatory Structural Zinc-binding Domain*S⃞

PubMed Central

Bottomley, Matthew J.; Lo Surdo, Paola; Di Giovine, Paolo; Cirillo, Agostino; Scarpelli, Rita; Ferrigno, Federica; Jones, Philip; Neddermann, Petra; De Francesco, Raffaele; Steinkühler, Christian; Gallinari, Paola; Carfí, Andrea

2008-01-01

Histone deacetylases (HDACs) regulate chromatin status and gene expression, and their inhibition is of significant therapeutic interest. To date, no biological substrate for class IIa HDACs has been identified, and only low activity on acetylated lysines has been demonstrated. Here, we describe inhibitor-bound and inhibitor-free structures of the histone deacetylase-4 catalytic domain (HDAC4cd) and of an HDAC4cd active site mutant with enhanced enzymatic activity toward acetylated lysines. The structures presented, coupled with activity data, provide the molecular basis for the intrinsically low enzymatic activity of class IIa HDACs toward acetylated lysines and reveal active site features that may guide the design of class-specific inhibitors. In addition, these structures reveal a conformationally flexible structural zinc-binding domain conserved in all class IIa enzymes. Importantly, either the mutation of residues coordinating the structural zinc ion or the binding of a class IIa selective inhibitor prevented the association of HDAC4 with the N-CoR·HDAC3 repressor complex. Together, these data suggest a key role of the structural zinc-binding domain in the regulation of class IIa HDAC functions. PMID:18614528

Active myocarditis in a patient with chronic active Epstein-Barr virus infection.

PubMed

Takano, Hiroyuki; Nakagawa, Keiichi; Ishio, Naoki; Daimon, Michiko; Daimon, Masao; Kobayashi, Yoshio; Hiroshima, Kenzo; Komuro, Issei

2008-10-30

Chronic active Epstein-Barr virus (CAEBV) infection is characterized by chronic or recurrent infectious mononucleosis-like symptoms and the prognosis of CAEBV infection is quite poor. The incidence of myocarditis as a complication of EBV infection is not so high and it is unusual that heart failure appears as the initial symptom. However, it is very important to detect and treat chronic active myocarditis in the early phase of CAEBV infection because chronic active myocarditis disorganizes and decreases cardiomyocytes, resulting in the progression to heart failure. We report a case of a 45-year-old man with CAEBV infection for 5 years. Echocardiography revealed moderate left ventricular systolic dysfunction with mild pericardial effusion. Endomyocardial biopsies demonstrated massive lymphocytic infiltration with adjacent myocytolysis and necrosis of cardiomyocytes suggesting active myocarditis. Immunohistological analysis of biopsies revealed that the infiltrating cells were mainly T lymphocytes. And some of the infiltrating cells showed a positive signal for the EBV-encoded small nuclear RNA by in situ hybridization. Positron emission tomography using (18)F-fluoro-2-deoxyglucose ((18)F-FDG) performed revealed increased uptake of (18)F-FDG of whole left ventricular wall with mild heterogeneity.

Structural and functional analysis of the human HDAC4 catalytic domain reveals a regulatory structural zinc-binding domain.

PubMed

Bottomley, Matthew J; Lo Surdo, Paola; Di Giovine, Paolo; Cirillo, Agostino; Scarpelli, Rita; Ferrigno, Federica; Jones, Philip; Neddermann, Petra; De Francesco, Raffaele; Steinkühler, Christian; Gallinari, Paola; Carfí, Andrea

2008-09-26

Histone deacetylases (HDACs) regulate chromatin status and gene expression, and their inhibition is of significant therapeutic interest. To date, no biological substrate for class IIa HDACs has been identified, and only low activity on acetylated lysines has been demonstrated. Here, we describe inhibitor-bound and inhibitor-free structures of the histone deacetylase-4 catalytic domain (HDAC4cd) and of an HDAC4cd active site mutant with enhanced enzymatic activity toward acetylated lysines. The structures presented, coupled with activity data, provide the molecular basis for the intrinsically low enzymatic activity of class IIa HDACs toward acetylated lysines and reveal active site features that may guide the design of class-specific inhibitors. In addition, these structures reveal a conformationally flexible structural zinc-binding domain conserved in all class IIa enzymes. Importantly, either the mutation of residues coordinating the structural zinc ion or the binding of a class IIa selective inhibitor prevented the association of HDAC4 with the N-CoR.HDAC3 repressor complex. Together, these data suggest a key role of the structural zinc-binding domain in the regulation of class IIa HDAC functions.

Gene expression profiling in equine polysaccharide storage myopathy revealed inflammation, glycogenesis inhibition, hypoxia and mitochondrial dysfunctions.

PubMed

Barrey, Eric; Mucher, Elodie; Jeansoule, Nicolas; Larcher, Thibaut; Guigand, Lydie; Herszberg, Bérénice; Chaffaux, Stéphane; Guérin, Gérard; Mata, Xavier; Benech, Philippe; Canale, Marielle; Alibert, Olivier; Maltere, Péguy; Gidrol, Xavier

2009-08-07

Several cases of myopathies have been observed in the horse Norman Cob breed. Muscle histology examinations revealed that some families suffer from a polysaccharide storage myopathy (PSSM). It is assumed that a gene expression signature related to PSSM should be observed at the transcriptional level because the glycogen storage disease could also be linked to other dysfunctions in gene regulation. Thus, the functional genomic approach could be conducted in order to provide new knowledge about the metabolic disorders related to PSSM. We propose exploring the PSSM muscle fiber metabolic disorders by measuring gene expression in relationship with the histological phenotype. Genotypying analysis of GYS1 mutation revealed 2 homozygous (AA) and 5 heterozygous (GA) PSSM horses. In the PSSM muscles, histological data revealed PAS positive amylase resistant abnormal polysaccharides, inflammation, necrosis, and lipomatosis and active regeneration of fibers. Ultrastructural evaluation revealed a decrease of mitochondrial number and structural disorders. Extensive accumulation of an abnormal polysaccharide displaced and partially replaced mitochondria and myofibrils. The severity of the disease was higher in the two homozygous PSSM horses.Gene expression analysis revealed 129 genes significantly modulated (p < 0.05). The following genes were up-regulated over 2 fold: IL18, CTSS, LUM, CD44, FN1, GST01. The most down-regulated genes were the following: mitochondrial tRNA, SLC2A2, PRKCalpha, VEGFalpha. Data mining analysis showed that protein synthesis, apoptosis, cellular movement, growth and proliferation were the main cellular functions significantly associated with the modulated genes (p < 0.05). Several up-regulated genes, especially IL18, revealed a severe muscular inflammation in PSSM muscles. The up-regulation of glycogen synthase kinase-3 (GSK3beta) under its active form could be responsible for glycogen synthase (GYS1) inhibition and hypoxia-inducible factor (HIF1alpha) destabilization. The main disorders observed in PSSM muscles could be related to mitochondrial dysfunctions, glycogenesis inhibition and the chronic hypoxia of the PSSM muscles.

Trace metal depositional patterns from an open pit mining activity as revealed by archived avian gizzard contents.

PubMed

Bendell, L I

2011-02-15

Archived samples of blue grouse (Dendragapus obscurus) gizzard contents, inclusive of grit, collected yearly between 1959 and 1970 were analyzed for cadmium, lead, zinc, and copper content. Approximately halfway through the 12-year sampling period, an open-pit copper mine began activities, then ceased operations 2 years later. Thus the archived samples provided a unique opportunity to determine if avian gizzard contents, inclusive of grit, could reveal patterns in the anthropogenic deposition of trace metals associated with mining activities. Gizzard concentrations of cadmium and copper strongly coincided with the onset of opening and the closing of the pit mining activity. Gizzard zinc and lead demonstrated significant among year variation; however, maximum concentrations did not correlate to mining activity. The archived gizzard contents did provide a useful tool for documenting trends in metal depositional patterns related to an anthropogenic activity. Further, blue grouse ingesting grit particles during the time of active mining activity would have been exposed to toxicologically significant levels of cadmium. Gizzard lead concentrations were also of toxicological significance but not related to mining activity. This type of "pulse" toxic metal exposure as a consequence of open-pit mining activity would not necessarily have been revealed through a "snap-shot" of soil, plant or avian tissue trace metal analysis post-mining activity. Copyright © 2010 Elsevier B.V. All rights reserved.

Iron meteorite fragment studied by atomic and nuclear analytical methods

NASA Astrophysics Data System (ADS)

Cesnek, Martin; Štefánik, Milan; Kmječ, Tomáš; Miglierini, Marcel

2016-10-01

Chemical and structural compositions of a fragment of Sikhote-Alin iron meteorite were investigated by X-ray fluorescence analysis (XRF), neutron activation analysis (NAA) and Mössbauer spectroscopy (MS). XRF and NAA revealed the presence of chemical elements which are characteristic for iron meteorites. XRF also showed a significant amount of Si and Al on the surface of the fragment. MS spectra revealed possible presence of α-Fe(Ni, Co) phase with different local Ni concentration. Furthermore, paramagnetic singlet was detected in Mössbauer spectra recorded at room temperature and at 4.2 K.

Quantitative Proteomics of the Tonoplast Reveals a Role for Glycolytic Enzymes in Salt Tolerance[C][W

PubMed Central

Barkla, Bronwyn J.; Vera-Estrella, Rosario; Hernández-Coronado, Marcela; Pantoja, Omar

2009-01-01

To examine the role of the tonoplast in plant salt tolerance and identify proteins involved in the regulation of transporters for vacuolar Na+ sequestration, we exploited a targeted quantitative proteomics approach. Two-dimensional differential in-gel electrophoresis analysis of free flow zonal electrophoresis separated tonoplast fractions from control, and salt-treated Mesembryanthemum crystallinum plants revealed the membrane association of glycolytic enzymes aldolase and enolase, along with subunits of the vacuolar H+-ATPase V-ATPase. Protein blot analysis confirmed coordinated salt regulation of these proteins, and chaotrope treatment indicated a strong tonoplast association. Reciprocal coimmunoprecipitation studies revealed that the glycolytic enzymes interacted with the V-ATPase subunit B VHA-B, and aldolase was shown to stimulate V-ATPase activity in vitro by increasing the affinity for ATP. To investigate a physiological role for this association, the Arabidopsis thaliana cytoplasmic enolase mutant, los2, was characterized. These plants were salt sensitive, and there was a specific reduction in enolase abundance in the tonoplast from salt-treated plants. Moreover, tonoplast isolated from mutant plants showed an impaired ability for aldolase stimulation of V-ATPase hydrolytic activity. The association of glycolytic proteins with the tonoplast may not only channel ATP to the V-ATPase, but also directly upregulate H+-pump activity. PMID:20028841

Quantitative proteomics of the tonoplast reveals a role for glycolytic enzymes in salt tolerance.

PubMed

Barkla, Bronwyn J; Vera-Estrella, Rosario; Hernández-Coronado, Marcela; Pantoja, Omar

2009-12-01

To examine the role of the tonoplast in plant salt tolerance and identify proteins involved in the regulation of transporters for vacuolar Na(+) sequestration, we exploited a targeted quantitative proteomics approach. Two-dimensional differential in-gel electrophoresis analysis of free flow zonal electrophoresis separated tonoplast fractions from control, and salt-treated Mesembryanthemum crystallinum plants revealed the membrane association of glycolytic enzymes aldolase and enolase, along with subunits of the vacuolar H(+)-ATPase V-ATPase. Protein blot analysis confirmed coordinated salt regulation of these proteins, and chaotrope treatment indicated a strong tonoplast association. Reciprocal coimmunoprecipitation studies revealed that the glycolytic enzymes interacted with the V-ATPase subunit B VHA-B, and aldolase was shown to stimulate V-ATPase activity in vitro by increasing the affinity for ATP. To investigate a physiological role for this association, the Arabidopsis thaliana cytoplasmic enolase mutant, los2, was characterized. These plants were salt sensitive, and there was a specific reduction in enolase abundance in the tonoplast from salt-treated plants. Moreover, tonoplast isolated from mutant plants showed an impaired ability for aldolase stimulation of V-ATPase hydrolytic activity. The association of glycolytic proteins with the tonoplast may not only channel ATP to the V-ATPase, but also directly upregulate H(+)-pump activity.

Mesoscale Variability in SUCCESS Data

NASA Technical Reports Server (NTRS)

Eckermann, Stephen D.

1998-01-01

Analysis of meteorological, chemical, and microphysical data from the airborne SUCCESS mission is reported. Careful analysis of the complex DC-8 flight pattern of May 2, 1996 reveals 19 linear or nearly linear flight segments within six main geographical areas, which we have analyzed. Significant mountain wave activity is revealed in the data from the MMS and MTP instruments on the DC-8, which resembles previous observations of mountain wave structures near Boulder, CO. Strong mountain-wave-induced upwelling downwind of the Rockies is noted. Turbulence is also noted in regions of the mountain wave consistent with overturning near the tropopause. Zonal winds recorded on the ER-2 are shown to consistent with mountain wave breaking at or near critical levels in the stratosphere, consistent with the strong turbulence reported by the pilot during the ER-2 flight. Those observations have been supported with spectral analyses and modeling studies. "Postcasts" of mountain wave activity on May 2, 1996, using the Naval Research Laboratory Mountain Wave Forecast Model (NRL/MWFM) predicts both strong mountain wave activity near the tropopause (as measured by the DC-8) and strong mountain-wave-induced turbulence in the stratosphere (as encountered by the ER-2). Two-dimensional simulations of fluid flow over topography reveal similar isentropic structures to observations.

Genome-Based Metabolic Mapping and 13C Flux Analysis Reveal Systematic Properties of an Oleaginous Microalga Chlorella protothecoides

DOE PAGES

Wu, Chao; Xiong, Wei; Dai, Junbiao; ...

2014-12-15

We report that integrated and genome-based flux balance analysis, metabolomics, and 13C-label profiling of phototrophic and heterotrophic metabolism in Chlorella protothecoides, an oleaginous green alga for biofuel. The green alga Chlorella protothecoides, capable of autotrophic and heterotrophic growth with rapid lipid synthesis, is a promising candidate for biofuel production. Based on the newly available genome knowledge of the alga, we reconstructed the compartmentalized metabolic network consisting of 272 metabolic reactions, 270 enzymes, and 461 encoding genes and simulated the growth in different cultivation conditions with flux balance analysis. Phenotype-phase plane analysis shows conditions achieving theoretical maximum of the biomass andmore » corresponding fatty acid-producing rate for phototrophic cells (the ratio of photon uptake rate to CO 2 uptake rate equals 8.4) and heterotrophic ones (the glucose uptake rate to O 2 consumption rate reaches 2.4), respectively. Isotope-assisted liquid chromatography-mass spectrometry/mass spectrometry reveals higher metabolite concentrations in the glycolytic pathway and the tricarboxylic acid cycle in heterotrophic cells compared with autotrophic cells. We also observed enhanced levels of ATP, nicotinamide adenine dinucleotide (phosphate), reduced, acetyl-Coenzyme A, and malonyl-Coenzyme A in heterotrophic cells consistently, consistent with a strong activity of lipid synthesis. To profile the flux map in experimental conditions, we applied nonstationary 13C metabolic flux analysis as a complementing strategy to flux balance analysis. We found that the result reveals negligible photorespiratory fluxes and a metabolically low active tricarboxylic acid cycle in phototrophic C. protothecoides. In comparison, high throughput of amphibolic reactions and the tricarboxylic acid cycle with no glyoxylate shunt activities were measured for heterotrophic cells. Lastly, taken together, the metabolic network modeling assisted by experimental metabolomics and 13C labeling better our understanding on global metabolism of oleaginous alga, paving the way to the systematic engineering of the microalga for biofuel production.« less

CRISPR/Cas9 and active genetics-based trans-species replacement of the endogenous Drosophila kni-L2 CRM reveals unexpected complexity.

PubMed

Xu, Xiang-Ru Shannon; Gantz, Valentino Matteo; Siomava, Natalia; Bier, Ethan

2017-12-23

The knirps ( kni ) locus encodes transcription factors required for induction of the L2 wing vein in Drosophila . Here, we employ diverse CRISPR/Cas9 genome editing tools to generate a series of targeted lesions within the endogenous cis-regulatory module (CRM) required for kni expression in the L2 vein primordium. Phenotypic analysis of these ' in locus ' mutations based on both expression of Kni protein and adult wing phenotypes, reveals novel unexpected features of L2-CRM function including evidence for a chromosome pairing-dependent process that promotes transcription. We also demonstrate that self-propagating active genetic elements (CopyCat elements) can efficiently delete and replace the L2-CRM with orthologous sequences from other divergent fly species. Wing vein phenotypes resulting from these trans-species enhancer replacements parallel features of the respective donor fly species. This highly sensitive phenotypic readout of enhancer function in a native genomic context reveals novel features of CRM function undetected by traditional reporter gene analysis. © 2017, Xu et al.

CRISPR/Cas9 and active genetics-based trans-species replacement of the endogenous Drosophila kni-L2 CRM reveals unexpected complexity

PubMed Central

Siomava, Natalia

2017-01-01

The knirps (kni) locus encodes transcription factors required for induction of the L2 wing vein in Drosophila. Here, we employ diverse CRISPR/Cas9 genome editing tools to generate a series of targeted lesions within the endogenous cis-regulatory module (CRM) required for kni expression in the L2 vein primordium. Phenotypic analysis of these ‘in locus’ mutations based on both expression of Kni protein and adult wing phenotypes, reveals novel unexpected features of L2-CRM function including evidence for a chromosome pairing-dependent process that promotes transcription. We also demonstrate that self-propagating active genetic elements (CopyCat elements) can efficiently delete and replace the L2-CRM with orthologous sequences from other divergent fly species. Wing vein phenotypes resulting from these trans-species enhancer replacements parallel features of the respective donor fly species. This highly sensitive phenotypic readout of enhancer function in a native genomic context reveals novel features of CRM function undetected by traditional reporter gene analysis. PMID:29274230

Translational Advancement of Somatostatin Gene Delivery for Disease Modification and Cognitive Sparing in Intractable Epilepsy

DTIC Science & Technology

2015-09-01

morphological analysis revealed significantly more activated (p < 0.001) and highly activated ( phagocytic ; p < 0.05) microglia in the dentate gyri of...process with small cell bodies (Figure 10A). Activated microglia exhibit less ramified processes and larger nuclei (Figure 10B) and phagocytic microglia...significantly increases in the dentate gyri of kindled rats along with the total number of highly activated or phagocytic microglia. We are currently

Phosphoproteomic network analysis in the sea urchin Strongylocentrotus purpuratus reveals new candidates in egg activation.

PubMed

Guo, Hongbo; Garcia-Vedrenne, Ana Elisa; Isserlin, Ruth; Lugowski, Andrew; Morada, Anthony; Sun, Alex; Miao, Yishen; Kuzmanov, Uros; Wan, Cuihong; Ma, Hongyue; Foltz, Kathy; Emili, Andrew

2015-12-01

Fertilization triggers a dynamic symphony of molecular transformations induced by a rapid rise in intracellular calcium. Most prominent are surface alterations, metabolic activation, cytoskeletal reorganization, and cell-cycle reentry. While the activation process appears to be broadly evolutionarily conserved, and protein phosphorylation is known to play a key role, the signaling networks mediating the response to fertilization are not well described. To address this gap, we performed a time course phosphoproteomic analysis of egg activation in the sea urchin Strongylocentrotus purpuratus, a system that offers biochemical tractability coupled with exquisite synchronicity. By coupling large-scale phosphopeptide enrichment with unbiased quantitative MS, we identified striking changes in global phosphoprotein patterns at 2- and 5-min postfertilization as compared to unfertilized eggs. Overall, we mapped 8796 distinct phosphosite modifications on 2833 phosphoproteins, of which 15% were differentially regulated in early egg activation. Activated kinases were identified by phosphosite mapping, while enrichment analyses revealed conserved signaling cascades not previously associated with egg activation. This work represents the most comprehensive study of signaling associated with egg activation to date, suggesting novel mechanisms that can be experimentally tested and providing a valuable resource for the broader research community. All MS data have been deposited in the ProteomeXchange with identifier PXD002239 (http://proteomecentral.proteomexchange.org/dataset/PXD002239). © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Within-Subject Correlation Analysis to Detect Functional Areas Associated With Response Inhibition.

PubMed

Yamasaki, Tomoko; Ogawa, Akitoshi; Osada, Takahiro; Jimura, Koji; Konishi, Seiki

2018-01-01

Functional areas in fMRI studies are often detected by brain-behavior correlation, calculating across-subject correlation between the behavioral index and the brain activity related to a function of interest. Within-subject correlation analysis is also employed in a single subject level, which utilizes cognitive fluctuations in a shorter time period by correlating the behavioral index with the brain activity across trials. In the present study, the within-subject analysis was applied to the stop-signal task, a standard task to probe response inhibition, where efficiency of response inhibition can be evaluated by the stop-signal reaction time (SSRT). Since the SSRT is estimated, by definition, not in a trial basis but from pooled trials, the correlation across runs was calculated between the SSRT and the brain activity related to response inhibition. The within-subject correlation revealed negative correlations in the anterior cingulate cortex and the cerebellum. Moreover, the dissociation pattern was observed in the within-subject analysis when earlier vs. later parts of the runs were analyzed: negative correlation was dominant in earlier runs, whereas positive correlation was dominant in later runs. Regions of interest analyses revealed that the negative correlation in the anterior cingulate cortex, but not in the cerebellum, was dominant in earlier runs, suggesting multiple mechanisms associated with inhibitory processes that fluctuate on a run-by-run basis. These results indicate that the within-subject analysis compliments the across-subject analysis by highlighting different aspects of cognitive/affective processes related to response inhibition.

Psychosocial versus physiological stress – meta-analyses on deactivations and activations of the neural correlates of stress reactions

PubMed Central

Kogler, Lydia; Mueller, Veronika I.; Chang, Amy; Eickhoff, Simon B.; Fox, Peter T.; Gur, Ruben C.; Derntl, Birgit

2015-01-01

Stress is present in everyday life in various forms and situations. Two stressors frequently investigated are physiological and psychosocial stress. Besides similar subjective and hormonal responses, it has been suggested that they also share common neural substrates. The current study used activation-likelihood-estimation meta-analysis to test this assumption by integrating results of previous neuroimaging studies on stress processing. Reported results are cluster-level FWE corrected. The inferior frontal gyrus (IFG) and the anterior insula (AI) were the only regions that demonstrated overlapping activation for both stressors. Analysis of physiological stress showed consistent activation of cognitive and affective components of pain processing such as the insula, striatum, or the middle cingulate cortex. Contrarily, analysis across psychosocial stress revealed consistent activation of the right superior temporal gyrus and deactivation of the striatum. Notably, parts of the striatum appeared to be functionally specified: the dorsal striatum was activated in physiological stress, whereas the ventral striatum was deactivated in psychosocial stress. Additional functional connectivity and decoding analyses further characterized this functional heterogeneity and revealed higher associations of the dorsal striatum with motor regions and of the ventral striatum with reward processing. Based on our meta-analytic approach, activation of the IFG and the AI seems to indicate a global neural stress reaction. While physiological stress activates a motoric fight-or-flight reaction, during psychosocial stress attention is shifted towards emotion regulation and goal-directed behavior, and reward processing is reduced. Our results show the significance of differentiating physiological and psychosocial stress in neural engagement. Furthermore, the assessment of deactivations in addition to activations in stress research is highly recommended. PMID:26123376

Meta-analysis of human gene expression in response to Mycobacterium tuberculosis infection reveals potential therapeutic targets.

PubMed

Wang, Zhang; Arat, Seda; Magid-Slav, Michal; Brown, James R

2018-01-10

With the global emergence of multi-drug resistant strains of Mycobacterium tuberculosis, new strategies to treat tuberculosis are urgently needed such as therapeutics targeting potential human host factors. Here we performed a statistical meta-analysis of human gene expression in response to both latent and active pulmonary tuberculosis infections from nine published datasets. We found 1655 genes that were significantly differentially expressed during active tuberculosis infection. In contrast, no gene was significant for latent tuberculosis. Pathway enrichment analysis identified 90 significant canonical human pathways, including several pathways more commonly related to non-infectious diseases such as the LRRK2 pathway in Parkinson's disease, and PD-1/PD-L1 signaling pathway important for new immuno-oncology therapies. The analysis of human genome-wide association studies datasets revealed tuberculosis-associated genetic variants proximal to several genes in major histocompatibility complex for antigen presentation. We propose several new targets and drug-repurposing opportunities including intravenous immunoglobulin, ion-channel blockers and cancer immuno-therapeutics for development as combination therapeutics with anti-mycobacterial agents. Our meta-analysis provides novel insights into host genes and pathways important for tuberculosis and brings forth potential drug repurposing opportunities for host-directed therapies.

Predicting risky choices from brain activity patterns

PubMed Central

Helfinstein, Sarah M.; Schonberg, Tom; Congdon, Eliza; Karlsgodt, Katherine H.; Mumford, Jeanette A.; Sabb, Fred W.; Cannon, Tyrone D.; London, Edythe D.; Bilder, Robert M.; Poldrack, Russell A.

2014-01-01

Previous research has implicated a large network of brain regions in the processing of risk during decision making. However, it has not yet been determined if activity in these regions is predictive of choices on future risky decisions. Here, we examined functional MRI data from a large sample of healthy subjects performing a naturalistic risk-taking task and used a classification analysis approach to predict whether individuals would choose risky or safe options on upcoming trials. We were able to predict choice category successfully in 71.8% of cases. Searchlight analysis revealed a network of brain regions where activity patterns were reliably predictive of subsequent risk-taking behavior, including a number of regions known to play a role in control processes. Searchlights with significant predictive accuracy were primarily located in regions more active when preparing to avoid a risk than when preparing to engage in one, suggesting that risk taking may be due, in part, to a failure of the control systems necessary to initiate a safe choice. Additional analyses revealed that subject choice can be successfully predicted with minimal decrements in accuracy using highly condensed data, suggesting that information relevant for risky choice behavior is encoded in coarse global patterns of activation as well as within highly local activation within searchlights. PMID:24550270

Analysis of climate and anthropogenic impacts on runoff in the Lower Pra River Basin of Ghana.

PubMed

Awotwi, Alfred; Anornu, Geophrey Kwame; Quaye-Ballard, Jonathan; Annor, Thompson; Forkuo, Eric Kwabena

2017-12-01

The Lower Pra River Basin (LPRB), located in the forest zone of southern Ghana has experienced changes due to variability in precipitation and diverse anthropogenic activities. Therefore, to maintain the functions of the ecosystem for water resources management, planning and sustainable development, it is important to differentiate the impacts of precipitation variability and anthropogenic activities on stream flow changes. We investigated the variability in runoff and quantified the contributions of precipitation and anthropogenic activities on runoff at the LPRB. Analysis of the precipitation-runoff for the period 1970-2010 revealed breakpoints in 1986, 2000, 2004 and 2010 in the LPRB. The periods influenced by anthropogenic activities were categorized into three periods 1987-2000, 2001-2004 and 2005-2010, revealing a decrease in runoff during 1987-2000 and an increase in runoff during 2001-2004 and 2005-2010. Assessment of monthly, seasonal and annual runoff depicted a significant increasing trend in the runoff time series during the dry season. Generally, runoff increased at a rate of 9.98 × 10 7 m 3 yr -1 , with precipitation variability and human activities contributing 17.4% and 82.3% respectively. The dominant small scale alluvial gold mining activity significantly contributes to the net runoff variability in LPRB.

Forming a negative impression of another person correlates with activation in medial prefrontal cortex and amygdala.

PubMed

Iidaka, Tetsuya; Harada, Tokiko; Sadato, Norihiro

2011-09-01

Neural correlates involved in the formation of negative impression from face were investigated using event-related functional magnetic resonance imaging and a partial conditioning paradigm. Eighteen normal volunteers underwent imaging while they viewed the faces of two unfamiliar individuals: one individual's face was partially accompanied by negative emotion but the other's was not. After the volunteers learned the relationship between the faces and the emotion, they formed a more negative impression of the person's face when the emotion was presented. Subtraction analysis of the individuals' neutral faces revealed activation in the dorsal anterior cingulate cortex and superior temporal sulcus, but this activity did not correlate with the change of impression from face. On the other hand, the response in the left amygdala negatively correlated with the change of impression from face in the first run. Time modulation analysis revealed that activity in the dorsomedial prefrontal cortex associated with negative emotion was the largest in the initial part of the acquisition. These results suggest that a negative impression from face may be formed by orchestrated activity in the dorsomedial prefrontal cortex, dorsal anterior cingulate cortex and amygdala, and that the activity has a prominent role in the initial acquisition of negative emotion.

Astrophysics: The MAD world of black holes

NASA Astrophysics Data System (ADS)

Gabuzda, Denise

2014-06-01

An analysis of optical and radio observations has revealed how powerful jets are launched from the centres of active galaxies, where supermassive black holes accrete matter through magnetically arrested disks, or MADs. See Letter p.126

Stuttering as a trait or state - an ALE meta-analysis of neuroimaging studies.

PubMed

Belyk, Michel; Kraft, Shelly Jo; Brown, Steven

2015-01-01

Stuttering is a speech disorder characterised by repetitions, prolongations and blocks that disrupt the forward movement of speech. An earlier meta-analysis of brain imaging studies of stuttering (Brown et al., 2005) revealed a general trend towards rightward lateralization of brain activations and hyperactivity in the larynx motor cortex bilaterally. The present study sought not only to update that meta-analysis with recent work but to introduce an important distinction not present in the first study, namely the difference between 'trait' and 'state' stuttering. The analysis of trait stuttering compares people who stutter (PWS) with people who do not stutter when behaviour is controlled for, i.e., when speech is fluent in both groups. In contrast, the analysis of state stuttering examines PWS during episodes of stuttered speech compared with episodes of fluent speech. Seventeen studies were analysed using activation likelihood estimation. Trait stuttering was characterised by the well-known rightward shift in lateralization for language and speech areas. State stuttering revealed a more diverse pattern. Abnormal activation of larynx and lip motor cortex was common to the two analyses. State stuttering was associated with overactivation in the right hemisphere larynx and lip motor cortex. Trait stuttering was associated with overactivation of lip motor cortex in the right hemisphere but underactivation of larynx motor cortex in the left hemisphere. These results support a large literature highlighting laryngeal and lip involvement in the symptomatology of stuttering, and disambiguate two possible sources of activation in neuroimaging studies of persistent developmental stuttering. © 2014 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

Transcriptome responses in the rectal gland of fed and fasted spiny dogfish shark (Squalus acanthias) determined by suppression subtractive hybridization.

PubMed

Deck, Courtney A; McKay, Sheldon J; Fiedler, Tristan J; LeMoine, Christophe M R; Kajimura, Makiko; Nawata, C Michele; Wood, Chris M; Walsh, Patrick J

2013-12-01

Prior studies of the elasmobranch rectal gland have demonstrated that feeding induces profound and rapid up regulation of the gland's ability to secrete concentrated NaCl solutions and the metabolic capacity to support this highly ATP consuming process. We undertook the current study to attempt to determine the degree to which up regulation of mRNA transcription was involved in the gland's activation. cDNA libraries were created from mRNA isolated from rectal glands of fasted (7days post-feeding) and fed (6h and 22h post-feeding) spiny dogfish sharks (Squalus acanthias), and the libraries were subjected to suppression subtractive hybridization (SSH) analysis. Quantitative real time PCR (qPCR) was also used to ascertain the mRNA expression of several genes revealed by the SSH analysis. In total the treatments changed the abundance of 170 transcripts, with 103 up regulated by feeding, and 67 up regulated by fasting. While many of the changes took place in 'expected' Gene Ontology (GO) categories (e.g., metabolism, transport, structural proteins, DNA and RNA turnover, etc.), KEGG analysis revealed a number of categories which identify oxidative stress as a topic of interest for the gland. GO analysis also revealed that branched chain essential amino acids (e.g., valine, leucine, isoleucine) are potential metabolic fuels for the rectal gland. In addition, up regulation of transcripts for many genes in the anticipated GO categories did not agree (i.e., fasting down regulated in feeding treatments) with previously observed increases in their respective proteins/enzyme activities. These results suggest an 'anticipatory' storage of selected mRNAs which presumably supports the rapid translation of proteins upon feeding activation of the gland. © 2013 Elsevier Inc. All rights reserved.

Single-Pixel Optical Fluctuation Analysis of Calcium Channel Function in Active Zones of Motor Nerve Terminals

PubMed Central

Luo, Fujun; Dittrich, Markus; Stiles, Joel R.; Meriney, Stephen D.

2011-01-01

We used high-resolution fluorescence imaging and single-pixel optical fluctuation analysis to estimate the opening probability of individual voltage-gated calcium (Ca2+) channels during an action potential and the number of such Ca2+ channels within active zones of frog neuromuscular junctions. Analysis revealed ~36 Ca2+ channels within each active zone, similar to the number of docked synaptic vesicles but far less than the total number of transmembrane particles reported based on freeze-fracture analysis (~200–250). The probability that each channel opened during an action potential was only ~0.2. These results suggest why each active zone averages only one quantal release event during every other action potential, despite a substantial number of docked vesicles. With sparse Ca2+ channels and low opening probability, triggering of fusion for each vesicle is primarily controlled by Ca2+ influx through individual Ca2+ channels. In contrast, the entire synapse is highly reliable because it contains hundreds of active zones. PMID:21813687

A novel method for isolating podocytes using magnetic activated cell sorting.

PubMed

Murakami, Ayumi; Oshiro, Hisashi; Kanzaki, Seiichi; Yamaguchi, Akira; Yamanaka, Shoji; Furuya, Mitsuko; Miura, Satoshi; Kanno, Hiroshi; Nagashima, Yoji; Aoki, Ichiro; Nagahama, Kiyotaka

2010-12-01

A large body of accumulated data has now revealed that podocytes play a major role in the development of proteinuria. However, the mechanisms of podocyte injury, leading to foot process effacement and proteinuria, are still unclear partly due to the current lack of an appropriate strategy for preparing podocytes. In this study, we have developed a novel method of rapid isolation of podocytes from mice using magnetic activated cell sorting with an anti-nephrin antibody. After endothelial cell depletion using anti-CD31 antibody, nephrin-positive cells were prepared from mouse kidneys using magnetic activated cell sorting with polyclonal rabbit anti-nephrin antibody. Purity of the positively sorted cells was determined by confocal microscopy and fluorescence-activated cell sorting (FACS) analysis. Expression profiles of podocyte-specific molecules in the sorted fractions were characterized by qualitative PCR and immunoblot analysis. Nephrin-positive cells, isolated from mouse kidneys within 6 h, showed dual positivity for synaptopodin and rabbit IgG on confocal microscopy. FACS analysis revealed that the purity of the positively sorted fractions was ∼75%. The nephrin-positive cells sorted by this approach showed a significantly higher expression of podocyte-specific molecules compared with nephrin-negative fractions. These data strongly suggest that our novel method for isolating podocytes has great utility for various downstream applications such as genomic analysis, proteomics and transcriptomics to elucidate molecular profiling of podocyte biology in vivo compared with conventional methods as our approach requires only several hours to complete and no tissue culture.

EDS1 contributes to nonhost resistance of Arabidopsis thaliana against Erwinia amylovora.

PubMed

Moreau, Manon; Degrave, Alexandre; Vedel, Régine; Bitton, Frédérique; Patrit, Oriane; Renou, Jean-Pierre; Barny, Marie-Anne; Fagard, Mathilde

2012-03-01

Erwinia amylovora causes fire blight in rosaceous plants. In nonhost Arabidopsis thaliana, E. amylovora triggers necrotic symptoms associated with transient bacterial multiplication, suggesting either that A. thaliana lacks a susceptibility factor or that it actively restricts E. amylovora growth. Inhibiting plant protein synthesis at the time of infection led to an increase in necrosis and bacterial multiplication and reduced callose deposition, indicating that A. thaliana requires active protein synthesis to restrict E. amylovora growth. Analysis of the callose synthase-deficient pmr4-1 mutant indicated that lack of callose deposition alone did not lead to increased sensitivity to E. amylovora. Transcriptome analysis revealed that approximately 20% of the genes induced following E. amylovora infection are related to defense and signaling. Analysis of mutants affected in NDR1 and EDS1, two main components of the defense-gene activation observed, revealed that E. amylovora multiplied ten times more in the eds1-2 mutant than in the wild type but not in the ndr1-1 mutant. Analysis of mutants affected in three WRKY transcription factors showing EDS1-dependent activation identified WRKY46 and WRKY54 as positive regulators and WRKY70 as a negative regulator of defense against E. amylovora. Altogether, we show that EDS1 is a positive regulator of nonhost resistance against E. amylovora in A. thaliana and hypothesize that it controls the production of several effective defenses against E. amylovora through the action of WRKY46 and WRKY54, while WRKY70 acts as a negative regulator.

Comparison of biological activities of selenium and silver nanoparticles attached with bioactive phytoconstituents: green synthesized using Spermacoce hispida extract

NASA Astrophysics Data System (ADS)

Vennila, Krishnan; Chitra, Loganathan; Balagurunathan, Rama; Palvannan, Thayumanavan

2018-03-01

Selenium and silver nanoparticles (NPs) were synthesized using Spermacoce hispida aqueous leaf extract (Sh-ALE). The optimum condition required for the synthesis of Sh-SeNPs was found to be 30 mM selenious acid solution to Sh-ALE at the ratio of 4:46, pH 9, incubated at 40 °C for 10 min. On the other hand, for Sh-AgNPs the optimum condition was found to be 1 mM AgNO3 to the Sh-ALE solution at the ratio of 4:46, pH 8, incubated at 40 °C for 10 min. SEM analysis revealed that both the Sh-AgNPs and Sh-SeNPs are predominantly rod-shaped. Sh-SeNPs and Sh-AgNPs were found to possess concentration-dependent antioxidant activity. However, Sh-SeNPs showed potent anti-inflammatory property, antibacterial property and anticancer activity against human cervical cancer cell in comparison to Sh-AgNPs. Phytochemical analysis, FTIR and GC-MS analysis showed that various flavonoids, saponins and phenolic compounds present in Sh-ALE catalysed the formation of NPs. Also, GC-MS analysis revealed that Sh-SeNPs are capped by synaptogenin B and derivatives of apigenin, quinoline and quinazoline. The advantage of attachment of such phytoconstituents on Sh-SeNPs for its potent biological activity in comparison to Sh-AgNPs is evident in in vitro conditions.

Structure of the apoptosome: mechanistic insights into activation of an initiator caspase from Drosophila

PubMed Central

Pang, Yuxuan; Bai, Xiao-chen; Yan, Chuangye; Hao, Qi; Chen, Zheqin; Wang, Jia-Wei

2015-01-01

Apoptosis is executed by a cascade of caspase activation. The autocatalytic activation of an initiator caspase, exemplified by caspase-9 in mammals or its ortholog, Dronc, in fruit flies, is facilitated by a multimeric adaptor complex known as the apoptosome. The underlying mechanism by which caspase-9 or Dronc is activated by the apoptosome remains unknown. Here we report the electron cryomicroscopic (cryo-EM) structure of the intact apoptosome from Drosophila melanogaster at 4.0 Å resolution. Analysis of the Drosophila apoptosome, which comprises 16 molecules of the Dark protein (Apaf-1 ortholog), reveals molecular determinants that support the assembly of the 2.5-MDa complex. In the absence of dATP or ATP, Dronc zymogen potently induces formation of the Dark apoptosome, within which Dronc is efficiently activated. At 4.1 Å resolution, the cryo-EM structure of the Dark apoptosome bound to the caspase recruitment domain (CARD) of Dronc (Dronc-CARD) reveals two stacked rings of Dronc-CARD that are sandwiched between two octameric rings of the Dark protein. The specific interactions between Dronc-CARD and both the CARD and the WD40 repeats of a nearby Dark protomer are indispensable for Dronc activation. These findings reveal important mechanistic insights into the activation of initiator caspase by the apoptosome. PMID:25644603

Influence of Microtexture on Early Plastic Slip Activity in Ti-6Al-4V Polycrystals

NASA Astrophysics Data System (ADS)

Hémery, Samuel; Dang, Van Truong; Signor, Loïc; Villechaise, Patrick

2018-06-01

Microtextured regions are known to influence the fatigue performance of titanium alloys. Previous studies revealed that crack initiation, accounting for most of the fatigue life, is triggered by slip activity. The influence of microtextured regions on the early plastic slip activity was presently investigated by means of an in situ tensile test performed inside a scanning electron microscope on a bimodal Ti-6Al-4V polycrystalline specimen. A slip trace analysis was carried out in several regions with different crystallographic textures to highlight potentially different deformation behaviors. Significant stress heterogeneities were revealed through an early slip activation in microtextured regions with a predominant [0001] orientation. This point was shown to be related to a locally increased resolved shear stress. Consequences on behavior under cyclic loadings are finally discussed.

Quantifying the influences of various ecological factors on land surface temperature of urban forests.

PubMed

Ren, Yin; Deng, Lu-Ying; Zuo, Shu-Di; Song, Xiao-Dong; Liao, Yi-Lan; Xu, Cheng-Dong; Chen, Qi; Hua, Li-Zhong; Li, Zheng-Wei

2016-09-01

Identifying factors that influence the land surface temperature (LST) of urban forests can help improve simulations and predictions of spatial patterns of urban cool islands. This requires a quantitative analytical method that combines spatial statistical analysis with multi-source observational data. The purpose of this study was to reveal how human activities and ecological factors jointly influence LST in clustering regions (hot or cool spots) of urban forests. Using Xiamen City, China from 1996 to 2006 as a case study, we explored the interactions between human activities and ecological factors, as well as their influences on urban forest LST. Population density was selected as a proxy for human activity. We integrated multi-source data (forest inventory, digital elevation models (DEM), population, and remote sensing imagery) to develop a database on a unified urban scale. The driving mechanism of urban forest LST was revealed through a combination of multi-source spatial data and spatial statistical analysis of clustering regions. The results showed that the main factors contributing to urban forest LST were dominant tree species and elevation. The interactions between human activity and specific ecological factors linearly or nonlinearly increased LST in urban forests. Strong interactions between elevation and dominant species were generally observed and were prevalent in either hot or cold spots areas in different years. In conclusion, quantitative studies based on spatial statistics and GeogDetector models should be conducted in urban areas to reveal interactions between human activities, ecological factors, and LST. Copyright © 2016 Elsevier Ltd. All rights reserved.

A Meta-Analysis of 25 Years of Mood-Creativity Research: Hedonic Tone, Activation, or Regulatory Focus?

ERIC Educational Resources Information Center

Baas, Matthijs; De Dreu, Carsten K. W.; Nijstad, Bernard A.

2008-01-01

This meta-analysis synthesized 102 effect sizes reflecting the relation between specific moods and creativity. Effect sizes overall revealed that positive moods produce more creativity than mood-neutral controls (r = 0.15), but no significant differences between negative moods and mood-neutral controls (r = -0.03) or between positive and negative…

Mechanistic and structural basis of bioengineered bovine Cathelicidin-5 with optimized therapeutic activity

NASA Astrophysics Data System (ADS)

Sahoo, Bikash R.; Maruyama, Kenta; Edula, Jyotheeswara R.; Tougan, Takahiro; Lin, Yuxi; Lee, Young-Ho; Horii, Toshihiro; Fujiwara, Toshimichi

2017-03-01

Peptide-drug discovery using host-defense peptides becomes promising against antibiotic-resistant pathogens and cancer cells. Here, we customized the therapeutic activity of bovine cathelicidin-5 targeting to bacteria, protozoa, and tumor cells. The membrane dependent conformational adaptability and plasticity of cathelicidin-5 is revealed by biophysical analysis and atomistic simulations over 200 μs in thymocytes, leukemia, and E. coli cell-membranes. Our understanding of energy-dependent cathelicidin-5 intrusion in heterogeneous membranes aided in designing novel loss/gain-of-function analogues. In vitro findings identified leucine-zipper to phenylalanine substitution in cathelicidin-5 (1-18) significantly enhance the antimicrobial and anticancer activity with trivial hemolytic activity. Targeted mutants of cathelicidin-5 at kink region and N-terminal truncation revealed loss-of-function. We ensured the existence of a bimodal mechanism of peptide action (membranolytic and non-membranolytic) in vitro. The melanoma mouse model in vivo study further supports the in vitro findings. This is the first structural report on cathelicidin-5 and our findings revealed potent therapeutic application of designed cathelicidin-5 analogues.

Simultaneous inhibition of aryl hydrocarbon receptor (AhR) and Src abolishes androgen receptor signaling.

PubMed

Ghotbaddini, Maryam; Cisse, Keyana; Carey, Alexis; Powell, Joann B

2017-01-01

Altered c-Src activity has been strongly implicated in the development, growth, progression, and metastasis of human cancers including prostate cancer. Src is known to regulate several biological functions of tumor cells, including proliferation. There are several Src inhibitors under evaluation for clinical effectiveness but have shown little activity in monotherapy trials of solid tumors. Combination studies are being explored by in vitro analysis and in clinical trials. Here we investigate the effect of simultaneous inhibition of the aryl hydrocarbon receptor (AhR) and Src on androgen receptor (AR) signaling in prostate cancer cells. AhR has also been reported to interact with the Src signaling pathway during prostate development. c-Src protein kinase is associated with the AhR complex in the cytosol and upon ligand binding to AhR, c-Src is activated and released from the complex. AhR has also been shown to regulate AR signaling which remains functionally important in the development and progression of prostate cancer. We provide evidence that co-inhibition of AhR and Src abolish AR activity. Evaluation of total protein and cellular fractions revealed decreased pAR expression and AR nuclear localization. Assays utilizing an androgen responsive element (ARE) and qRT-PCR analysis of AR genes revealed decreased AR promoter activity and transcriptional activity in the presence of both AhR and Src inhibitors. Furthermore, co-inhibition of AhR and Src reduced the growth of prostate cancer cells compared to individual treatments. Several studies have revealed that AhR and Src individually inhibit cellular proliferation. However, this study is the first to suggest simultaneous inhibition of AhR and Src to inhibit AR signaling and prostate cancer cell growth.

Aberrant gene expression in mucosa adjacent to tumor reveals a molecular crosstalk in colon cancer

PubMed Central

2014-01-01

Background A colorectal tumor is not an isolated entity growing in a restricted location of the body. The patient’s gut environment constitutes the framework where the tumor evolves and this relationship promotes and includes a complex and tight correlation of the tumor with inflammation, blood vessels formation, nutrition, and gut microbiome composition. The tumor influence in the environment could both promote an anti-tumor or a pro-tumor response. Methods A set of 98 paired adjacent mucosa and tumor tissues from colorectal cancer (CRC) patients and 50 colon mucosa from healthy donors (246 samples in total) were included in this work. RNA extracted from each sample was hybridized in Affymetrix chips Human Genome U219. Functional relationships between genes were inferred by means of systems biology using both transcriptional regulation networks (ARACNe algorithm) and protein-protein interaction networks (BIANA software). Results Here we report a transcriptomic analysis revealing a number of genes activated in adjacent mucosa from CRC patients, not activated in mucosa from healthy donors. A functional analysis of these genes suggested that this active reaction of the adjacent mucosa was related to the presence of the tumor. Transcriptional and protein-interaction networks were used to further elucidate this response of normal gut in front of the tumor, revealing a crosstalk between proteins secreted by the tumor and receptors activated in the adjacent colon tissue; and vice versa. Remarkably, Slit family of proteins activated ROBO receptors in tumor whereas tumor-secreted proteins transduced a cellular signal finally activating AP-1 in adjacent tissue. Conclusions The systems-level approach provides new insights into the micro-ecology of colorectal tumorogenesis. Disrupting this intricate molecular network of cell-cell communication and pro-inflammatory microenvironment could be a therapeutic target in CRC patients. PMID:24597571

A multistate examination of partnership activity among local public health systems using the National Public Health Performance Standards.

PubMed

Barnes, Priscilla A; Curtis, Amy B; Hall-Downey, Laura; Moonesinghe, Ramal

2012-01-01

This study examines whether partnership-related measures in the second version of the National Public Health Performance Standards (NPHPS) are useful in evaluating level of activity as well as identifying latent constructs that exist among local public health systems (LPHSs). In a sample of 110 LPHSs, descriptive analysis was conducted to determine frequency and percentage of 18 partnership-related NPHPS measures. Principal components factor analysis was conducted to identify unobserved characteristics that promote effective partnerships among LPHSs. Results revealed that 13 of the 18 measures were most frequently reported at the minimal-moderate level (conducted 1%-49% of the time). Coordination of personal health and social services to optimize access (74.6%) was the most frequently reported measure at minimal-moderate levels. Optimal levels (conducted >75% of the time) were reported most frequently in 2 activities: participation in emergency preparedness coalitions and local health departments ensuring service provision by working with state health departments (67% and 61% of respondents, respectively) and the least optimally reported activity was review partnership effectiveness (4% of respondents). Factor analysis revealed categories of partnership-related measures in 4 domains: resources and activities contributing to relationship building, evaluating community leadership activities, research, and state and local linkages to support public health activities. System-oriented public health assessments may have questions that serve as proxy measures to examine levels of interorganizational partnerships. Several measures from the NPHPS were useful in establishing a national baseline of minimal and optimal activity levels as well as identifying factors to enhance the delivery of the 10 essential public health services among organizations and individuals in public health systems.

24/7 Operational Effectiveness Toolset: Mishap Investigation Interface

DTIC Science & Technology

2008-10-01

analysis software product. The toolset was based upon the Sleep, Activity, Fatigue, and Task Effectiveness (SAFTE™; Hursh et al., 2004). The SAFTE...meeting was for the purpose of requirements analysis , in which the designers elicited task information from the SMEs. The second meeting included a...investigators who also served as our SMEs. The requirements analysis revealed how fatigue related information is entered into the report of an Air Force

Rational design and validation of a vanilloid-sensitive TRPV2 ion channel.

PubMed

Yang, Fan; Vu, Simon; Yarov-Yarovoy, Vladimir; Zheng, Jie

2016-06-28

Vanilloids activation of TRPV1 represents an excellent model system of ligand-gated ion channels. Recent studies using cryo-electron microcopy (cryo-EM), computational analysis, and functional quantification revealed the location of capsaicin-binding site and critical residues mediating ligand-binding and channel activation. Based on these new findings, here we have successfully introduced high-affinity binding of capsaicin and resiniferatoxin to the vanilloid-insensitive TRPV2 channel, using a rationally designed minimal set of four point mutations (F467S-S498F-L505T-Q525E, termed TRPV2_Quad). We found that binding of resiniferatoxin activates TRPV2_Quad but the ligand-induced open state is relatively unstable, whereas binding of capsaicin to TRPV2_Quad antagonizes resiniferatoxin-induced activation likely through competition for the same binding sites. Using Rosetta-based molecular docking, we observed a common structural mechanism underlying vanilloids activation of TRPV1 and TRPV2_Quad, where the ligand serves as molecular "glue" that bridges the S4-S5 linker to the S1-S4 domain to open these channels. Our analysis revealed that capsaicin failed to activate TRPV2_Quad likely due to structural constraints preventing such bridge formation. These results not only validate our current working model for capsaicin activation of TRPV1 but also should help guide the design of drug candidate compounds for this important pain sensor.

Control and synchronisation of a novel seven-dimensional hyperchaotic system with active control

NASA Astrophysics Data System (ADS)

Varan, Metin; Akgul, Akif

2018-04-01

In this work, active control method is proposed for controlling and synchronising seven-dimensional (7D) hyperchaotic systems. The seven-dimensional hyperchaotic system is considered for the implementation. Seven-dimensional hyperchaotic system is also investigated via time series, phase portraits and bifurcation diagrams. For understanding the impact of active controllers on global asymptotic stability of synchronisation and control errors, the Lyapunov function is used. Numerical analysis is done to reveal the effectiveness of applied active control method and the results are discussed.

S. pombe Uba1-Ubc15 Structure Reveals a Novel Regulatory Mechanism of Ubiquitin E2 Activity.

PubMed

Lv, Zongyang; Rickman, Kimberly A; Yuan, Lingmin; Williams, Katelyn; Selvam, Shanmugam Panneer; Woosley, Alec N; Howe, Philip H; Ogretmen, Besim; Smogorzewska, Agata; Olsen, Shaun K

2017-02-16

Ubiquitin (Ub) E1 initiates the Ub conjugation cascade by activating and transferring Ub to tens of different E2s. How Ub E1 cooperates with E2s that differ substantially in their predicted E1-interacting residues is unknown. Here, we report the structure of S. pombe Uba1 in complex with Ubc15, a Ub E2 with intrinsically low E1-E2 Ub thioester transfer activity. The structure reveals a distinct Ubc15 binding mode that substantially alters the network of interactions at the E1-E2 interface compared to the only other available Ub E1-E2 structure. Structure-function analysis reveals that the intrinsically low activity of Ubc15 largely results from the presence of an acidic residue at its N-terminal region. Notably, Ub E2 N termini are serine/threonine rich in many other Ub E2s, leading us to hypothesize that phosphorylation of these sites may serve as a novel negative regulatory mechanism of Ub E2 activity, which we demonstrate biochemically and in cell-based assays. Copyright © 2017 Elsevier Inc. All rights reserved.

Computational Ranking of Yerba Mate Small Molecules Based on Their Predicted Contribution to Antibacterial Activity against Methicillin-Resistant Staphylococcus aureus

DOE PAGES

Rempe, Caroline S.; Burris, Kellie P.; Woo, Hannah L.; ...

2015-05-08

We report that the aqueous extract of yerba mate, a South American tea beverage made from Ilex paraguariensis leaves, has demonstrated bactericidal and inhibitory activity against bacterial pathogens, including methicillin-resistant Staphylococcus aureus (MRSA). The gas chromatography-mass spectrometry (GC-MS) analysis of two unique fractions of yerba mate aqueous extract revealed 8 identifiable small molecules in those fractions with antimicrobial activity. For a more comprehensive analysis, a data analysis pipeline was assembled to prioritize compounds for antimicrobial testing against both MRSA and methicillin-sensitive S. aureus using forty-two unique fractions of the tea extract that were generated in duplicate, assayed for activity, andmore » analyzed with GC-MS. As validation of our automated analysis, we checked our predicted active compounds for activity in literature references and used authentic standards to test for antimicrobial activity. 3,4-dihydroxybenzaldehyde showed the most antibacterial activity against MRSA at low concentrations in our bioassays. In addition, quinic acid and quercetin were identified using random forests analysis and 5-hydroxy pipecolic acid was identified using linear discriminant analysis. We also generated a ranked list of unidentified compounds that may contribute to the antimicrobial activity of yerba mate against MRSA. Here we utilized GC-MS data to implement an automated analysis that resulted in a ranked list of compounds that likely contribute to the antimicrobial activity of aqueous yerba mate extract against MRSA.« less

Computational Ranking of Yerba Mate Small Molecules Based on Their Predicted Contribution to Antibacterial Activity against Methicillin-Resistant Staphylococcus aureus

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rempe, Caroline S.; Burris, Kellie P.; Woo, Hannah L.

We report that the aqueous extract of yerba mate, a South American tea beverage made from Ilex paraguariensis leaves, has demonstrated bactericidal and inhibitory activity against bacterial pathogens, including methicillin-resistant Staphylococcus aureus (MRSA). The gas chromatography-mass spectrometry (GC-MS) analysis of two unique fractions of yerba mate aqueous extract revealed 8 identifiable small molecules in those fractions with antimicrobial activity. For a more comprehensive analysis, a data analysis pipeline was assembled to prioritize compounds for antimicrobial testing against both MRSA and methicillin-sensitive S. aureus using forty-two unique fractions of the tea extract that were generated in duplicate, assayed for activity, andmore » analyzed with GC-MS. As validation of our automated analysis, we checked our predicted active compounds for activity in literature references and used authentic standards to test for antimicrobial activity. 3,4-dihydroxybenzaldehyde showed the most antibacterial activity against MRSA at low concentrations in our bioassays. In addition, quinic acid and quercetin were identified using random forests analysis and 5-hydroxy pipecolic acid was identified using linear discriminant analysis. We also generated a ranked list of unidentified compounds that may contribute to the antimicrobial activity of yerba mate against MRSA. Here we utilized GC-MS data to implement an automated analysis that resulted in a ranked list of compounds that likely contribute to the antimicrobial activity of aqueous yerba mate extract against MRSA.« less

Structural snapshots of Xer recombination reveal activation by synaptic complex remodeling and DNA bending

PubMed Central

Bebel, Aleksandra; Karaca, Ezgi; Kumar, Banushree; Stark, W Marshall; Barabas, Orsolya

2016-01-01

Bacterial Xer site-specific recombinases play an essential genome maintenance role by unlinking chromosome multimers, but their mechanism of action has remained structurally uncharacterized. Here, we present two high-resolution structures of Helicobacter pylori XerH with its recombination site DNA difH, representing pre-cleavage and post-cleavage synaptic intermediates in the recombination pathway. The structures reveal that activation of DNA strand cleavage and rejoining involves large conformational changes and DNA bending, suggesting how interaction with the cell division protein FtsK may license recombination at the septum. Together with biochemical and in vivo analysis, our structures also reveal how a small sequence asymmetry in difH defines protein conformation in the synaptic complex and orchestrates the order of DNA strand exchanges. Our results provide insights into the catalytic mechanism of Xer recombination and a model for regulation of recombination activity during cell division. DOI: http://dx.doi.org/10.7554/eLife.19706.001 PMID:28009253

Mapping temporal dynamics in social interactions with unified structural equation modeling: A description and demonstration revealing time-dependent sex differences in play behavior

PubMed Central

Beltz, Adriene M.; Beekman, Charles; Molenaar, Peter C. M.; Buss, Kristin A.

2013-01-01

Developmental science is rich with observations of social interactions, but few available methodological and statistical approaches take full advantage of the information provided by these data. The authors propose implementation of the unified structural equation model (uSEM), a network analysis technique, for observational data coded repeatedly across time; uSEM captures the temporal dynamics underlying changes in behavior at the individual level by revealing the ways in which a single person influences – concurrently and in the future – other people. To demonstrate the utility of uSEM, the authors applied it to ratings of positive affect and vigor of activity during children’s unstructured laboratory play with unfamiliar, same-sex peers. Results revealed the time-dependent nature of sex differences in play behavior. For girls more than boys, positive affect was dependent upon peers’ prior positive affect. For boys more than girls, vigor of activity was dependent upon peers’ current vigor of activity. PMID:24039386

Coir fibre toxicity: in vivo and in vitro studies.

PubMed

Saxena, R P; Dogra, R K; Bhattacherjee, J W

1982-03-01

The biological activity of coir fibre, coir ash and their components were investigated in vitro by measuring the haemolytic activity and macrophage cytotoxicity. In vivo studies carried out by injecting guinea pigs intratracheally with coir fibres resulted in resolving granulomas. The observed haemolytic activity and macrophage cytotoxicity was more marked with coir ash compared with coir fibres. Chemical analysis of coir ash revealed the presence of toxic chemical constituents in appreciable amounts.

Eco-friendly preparation of zinc oxide nanoparticles using Tabernaemontana divaricata and its photocatalytic and antimicrobial activity.

PubMed

Raja, A; Ashokkumar, S; Pavithra Marthandam, R; Jayachandiran, J; Khatiwada, Chandra Prasad; Kaviyarasu, K; Ganapathi Raman, R; Swaminathan, M

2018-04-01

The present work reports the green synthesis of Zinc Oxide Nanoparticles (ZnO NPs) using aqueous Tabernaemontana divaricata green leaf extract. ZnO NPs have been characterized by X-ray diffraction (XRD), Ultra Violet-Visible (UV-Vis) studies, Scanning Electron Microscopy (SEM), Transmission Electron Microscopy (TEM) and Fourier Transform-Infra Red (FT-IR) analysis. XRD pattern analysis confirms the presence of pure hexagonal wurtzite crystalline structure of ZnO. The TEM images reveal the formation of spherical shape ZnO NPs with the sizes ranging from 20 to 50 nm. The FT-IR analysis suggests that the obtained ZnO NPs have been stabilized through the interactions of steroids, terpenoids, flavonoids, phenyl propanoids, phenolic acids and enzymes present in the leaf extract. Mechanism for the formation of ZnO NPs using Tabernaemontana divaricata as bioactive compound is proposed. As prepared ZnO NPs reveals antibacterial activity against three bacterial strains, Salmonella paratyphi, Escherichia coli and Staphylococcus aureus. The ZnO NPs shows higher antibacterial activity against S. aureus and E. coli and lesser antibacterial activity against S. paratyphi compared to the standard pharmaceutical formulation. Photocatalytic activity of synthesized ZnO NPs was analyzed for methylene blue (MB) dye degradation with sunlight. Almost complete degradation of dye occurred in 90 min. This nano-ZnO, prepared by eco-friendly method will be much useful for dye removal and bacterial decontamination. Copyright © 2018. Published by Elsevier B.V.

Evaluation of the toxicity and antimicrobial activity of hydroethanolic extract of Arrabidaea chica (Humb. & Bonpl.) B. Verl.

PubMed

Mafioleti, Luciano; da Silva Junior, Iberê Ferreira; Colodel, Edson Moleta; Flach, Adriana; Martins, Domingos Tabajara de Oliveira

2013-11-25

Arrabidaea chica (Bignoniaceae) is a vine native to the Amazon Rainforest, popularly known as "crajiru" and whose infusion and decoction of the leaves are used to treat diseases such as gastric ulcers, inflammations, infections, anemia, herpes, jaundice among others. It is also used as a natural dye. This work aimed to evaluate the in vitro and in vivo toxicity, antimicrobial activity including analysis of chemical constitution of the hydroethanolic extract of the leaves of Arrabidaea chica (HEAc). Acute and subchronic toxicity of HEAc was evaluated in mice and rats, respectively, and by Alamar blue (cytotoxicity assay) using CHO-K1 cells. Antimicrobial activity of HEAc was tested by broth microdilution method using a panel of bacteria and yeast of clinical interest. The preliminary phytochemical analysis of HEAc was performed by electrospray ionization mass spectrometry [ESI(+)-MS]. Secondary metabolites were quantified by colorimetric methods. When administered in vivo at doses up to 3000 mg/kg v.o., HEAc did not cause any signs and symptoms of acute toxicity in mice and no cytotoxicity in CHO-K1 cells. Administration for 30 days caused leukocytosis (200 mg/kg) and reversible reductions in non-dose dependent of body weight, total weight gain and feed intake in rats given 200mg/kg and 500 mg/kg of HEAc, but were not accompanied by behavioral and clinical changes (laboratory and histopathological) that may have demonstrated evidences of subchronic toxicity HEAc demonstrated a pronounced activity against Helicobacter pylori (MIC=12.5 μg/mL) and moderate activity against Enterococcus faecalis (MIC=100 μg/mL) in broth microdilution. Preliminary phytochemical analysis of HEAc by colorimetric methods revealed that mainly the presence of phenolic compounds (16.6%), especially flavones and flavonols (4.02%). [ESI(+)-MS] fingerprint analyses of HEAc revealed the presence of 3-deoxyanthocyanidins and kaempferol. Our data provide evidence that HEAc is safe and can be useful in infections related to Helicobacter pylori and Enterococcus faecalis. Phytochemical analysis revealed the predominant presence of flavones and flavonols, possibly involved in the antimicrobial action of HEAc. © 2013 Elsevier Ireland Ltd. All rights reserved.

Research Advances: Calorie Restriction and Increased Longevity Linked to Metabolic Changes; Isotope Ratios Reveal Trickery in the Produce Aisle; An Ancient Inca Tax and Metallurgy in Peru

ERIC Educational Resources Information Center

King, Angela G.

2007-01-01

The different lifelong patterns related to different levels of energy metabolism and the activities of the microbes in various animals are described. The analysis shows that many important beneficial changes occur due to the activities of symbiotic bacteria living in the intestinal tract.

How sensory-motor systems impact the neural organization for language: direct contrasts between spoken and signed language

PubMed Central

Emmorey, Karen; McCullough, Stephen; Mehta, Sonya; Grabowski, Thomas J.

2014-01-01

To investigate the impact of sensory-motor systems on the neural organization for language, we conducted an H215O-PET study of sign and spoken word production (picture-naming) and an fMRI study of sign and audio-visual spoken language comprehension (detection of a semantically anomalous sentence) with hearing bilinguals who are native users of American Sign Language (ASL) and English. Directly contrasting speech and sign production revealed greater activation in bilateral parietal cortex for signing, while speaking resulted in greater activation in bilateral superior temporal cortex (STC) and right frontal cortex, likely reflecting auditory feedback control. Surprisingly, the language production contrast revealed a relative increase in activation in bilateral occipital cortex for speaking. We speculate that greater activation in visual cortex for speaking may actually reflect cortical attenuation when signing, which functions to distinguish self-produced from externally generated visual input. Directly contrasting speech and sign comprehension revealed greater activation in bilateral STC for speech and greater activation in bilateral occipital-temporal cortex for sign. Sign comprehension, like sign production, engaged bilateral parietal cortex to a greater extent than spoken language. We hypothesize that posterior parietal activation in part reflects processing related to spatial classifier constructions in ASL and that anterior parietal activation may reflect covert imitation that functions as a predictive model during sign comprehension. The conjunction analysis for comprehension revealed that both speech and sign bilaterally engaged the inferior frontal gyrus (with more extensive activation on the left) and the superior temporal sulcus, suggesting an invariant bilateral perisylvian language system. We conclude that surface level differences between sign and spoken languages should not be dismissed and are critical for understanding the neurobiology of language. PMID:24904497

Functional analysis of Pacific oyster (Crassostrea gigas) β-thymosin: Focus on antimicrobial activity.

PubMed

Nam, Bo-Hye; Seo, Jung-Kil; Lee, Min Jeong; Kim, Young-Ok; Kim, Dong-Gyun; An, Cheul Min; Park, Nam Gyu

2015-07-01

An antimicrobial peptide, ∼5 kDa in size, was isolated and purified in its active form from the mantle of the Pacific oyster Crassostrea gigas by C18 reversed-phase high-performance liquid chromatography. Matrix-assisted laser desorption ionisation time-of-flight analysis revealed 4656.4 Da of the purified and unreduced peptide. A comparison of the N-terminal amino acid sequence of oyster antimicrobial peptide with deduced amino acid sequences in our local expressed sequence tag (EST) database of C. gigas (unpublished data) revealed that the oyster antimicrobial peptide sequence entirely matched the deduced amino acid sequence of an EST clone (HM-8_A04), which was highly homologous with the β-thymosin of other species. The cDNA possessed a 126-bp open reading frame that encoded a protein of 41 amino acids. To confirm the antimicrobial activity of C. gigas β-thymosin, we overexpressed a recombinant β-thymosin (rcgTβ) using a pET22 expression plasmid in an Escherichia coli system. The antimicrobial activity of rcgTβ was evaluated and demonstrated using a bacterial growth inhibition test in both liquid and solid cultures. Copyright © 2015 Elsevier Ltd. All rights reserved.

Identification of a mitochondrial alcohol dehydrogenase in Schizosaccharomyces pombe: new insights into energy metabolism

PubMed Central

Crichton, Paul G.; Affourtit, Charles; Moore, Anthony L.

2006-01-01

In the present study we have shown that mitochondria isolated from Schizosaccharomyces pombe exhibit antimycin A-sensitive oxygen uptake activity that is exclusively dependent on ethanol and is inhibited by trifluoroethanol, a potent inhibitor of ADH (alcohol dehydrogenase). Ethanol-dependent respiratory activity has, to our knowledge, not been reported in S. pombe mitochondria to date, which is surprising as it has been concluded previously that only one ADH gene, encoding a cytosolic enzyme, occurs in this yeast. Spectrophotometric enzyme assays reveal that ADH activity in isolated mitochondria is increased ∼16-fold by Triton X-100, which demonstrates that the enzyme is located in the matrix. Using genetic knockouts, we show conclusively that the novel mitochondrial ADH is encoded by adh4 and, as such, is unrelated to ADH isoenzymes found in mitochondria of other yeasts. By performing a modular-kinetic analysis of mitochondrial electron transfer, we furthermore show how ethanol-dependent respiratory activity (which involves oxidation of matrix-located NADH) compares with that observed when succinate or externally added NADH are used as substrates. This analysis reveals distinct kinetic differences between substrates which fully explain the lack of respiratory control generally observed during ethanol oxidation in yeast mitochondria. PMID:16999687

Abstract representations of associated emotions in the human brain.

PubMed

Kim, Junsuk; Schultz, Johannes; Rohe, Tim; Wallraven, Christian; Lee, Seong-Whan; Bülthoff, Heinrich H

2015-04-08

Emotions can be aroused by various kinds of stimulus modalities. Recent neuroimaging studies indicate that several brain regions represent emotions at an abstract level, i.e., independently from the sensory cues from which they are perceived (e.g., face, body, or voice stimuli). If emotions are indeed represented at such an abstract level, then these abstract representations should also be activated by the memory of an emotional event. We tested this hypothesis by asking human participants to learn associations between emotional stimuli (videos of faces or bodies) and non-emotional stimuli (fractals). After successful learning, fMRI signals were recorded during the presentations of emotional stimuli and emotion-associated fractals. We tested whether emotions could be decoded from fMRI signals evoked by the fractal stimuli using a classifier trained on the responses to the emotional stimuli (and vice versa). This was implemented as a whole-brain searchlight, multivoxel activation pattern analysis, which revealed successful emotion decoding in four brain regions: posterior cingulate cortex (PCC), precuneus, MPFC, and angular gyrus. The same analysis run only on responses to emotional stimuli revealed clusters in PCC, precuneus, and MPFC. Multidimensional scaling analysis of the activation patterns revealed clear clustering of responses by emotion across stimulus types. Our results suggest that PCC, precuneus, and MPFC contain representations of emotions that can be evoked by stimuli that carry emotional information themselves or by stimuli that evoke memories of emotional stimuli, while angular gyrus is more likely to take part in emotional memory retrieval. Copyright © 2015 the authors 0270-6474/15/355655-09$15.00/0.

Analysis of Slow-Wave Activity and Slow-Wave Oscillations Prior to Somnambulism

PubMed Central

Jaar, Olivier; Pilon, Mathieu; Carrier, Julie; Montplaisir, Jacques; Zadra, Antonio

2010-01-01

Study Objectivies: Several studies have investigated slow wave sleep EEG parameters, including slow-wave activity (SWA) in relation to somnambulism, but results have been both inconsistent and contradictory. The first goal of the present study was to conduct a quantitative analysis of sleepwalkers' sleep EEG by studying fluctuations in spectral power for delta (1-4 Hz) and slow delta (0.5-1 Hz) before the onset of somnambulistic episodes. A secondary aim was to detect slow-wave oscillations to examine changes in their amplitude and density prior to behavioral episodes. Participants: Twenty-two adult sleepwalkers were investigated polysomnographically following 25 h of sleep deprivation. Results: Analysis of patients' sleep EEG over the 200 sec prior to the episodes' onset revealed that the episodes were not preceded by a gradual increase in spectral power for either delta or slow delta over frontal, central, or parietal leads. However, time course comparisons revealed significant changes in the density of slow-wave oscillations as well as in very slow oscillations with significant increases occurring during the final 20 sec immediately preceding episode onset. Conclusions: The specificity of these sleep EEG parameters for the occurrence and diagnosis of NREM parasomnias remains to be determined. Citation: Jaar O; Pilon M; Carrier J; Montplaisir J; Zadra A. Analysis of slow-wave activity and slow-wave oscillations prior to somnambulism. SLEEP 2010;33(11):1511-1516. PMID:21102993

Perceived climate in physical activity settings.

PubMed

Gill, Diane L; Morrow, Ronald G; Collins, Karen E; Lucey, Allison B; Schultz, Allison M

2010-01-01

This study focused on the perceived climate for LGBT youth and other minority groups in physical activity settings. A large sample of undergraduates and a selected sample including student teachers/interns and a campus Pride group completed a school climate survey and rated the climate in three physical activity settings (physical education, organized sport, exercise). Overall, school climate survey results paralleled the results with national samples revealing high levels of homophobic remarks and low levels of intervention. Physical activity climate ratings were mid-range, but multivariate analysis of variation test (MANOVA) revealed clear differences with all settings rated more inclusive for racial/ethnic minorities and most exclusive for gays/lesbians and people with disabilities. The results are in line with national surveys and research suggesting sexual orientation and physical characteristics are often the basis for harassment and exclusion in sport and physical activity. The current results also indicate that future physical activity professionals recognize exclusion, suggesting they could benefit from programs that move beyond awareness to skills and strategies for creating more inclusive programs.

Parametric mapping using spectral analysis for 11C-PBR28 PET reveals neuroinflammation in mild cognitive impairment subjects.

PubMed

Fan, Zhen; Dani, Melanie; Femminella, Grazia D; Wood, Melanie; Calsolaro, Valeria; Veronese, Mattia; Turkheimer, Federico; Gentleman, Steve; Brooks, David J; Hinz, Rainer; Edison, Paul

2018-07-01

Neuroinflammation and microglial activation play an important role in amnestic mild cognitive impairment (MCI) and Alzheimer's disease. In this study, we investigated the spatial distribution of neuroinflammation in MCI subjects, using spectral analysis (SA) to generate parametric maps and quantify 11 C-PBR28 PET, and compared these with compartmental and other kinetic models of quantification. Thirteen MCI and nine healthy controls were enrolled in this study. Subjects underwent 11 C-PBR28 PET scans with arterial cannulation. Spectral analysis with an arterial plasma input function was used to generate 11 C-PBR28 parametric maps. These maps were then compared with regional 11 C-PBR28 V T (volume of distribution) using a two-tissue compartment model and Logan graphic analysis. Amyloid load was also assessed with 18 F-Flutemetamol PET. With SA, three component peaks were identified in addition to blood volume. The 11 C-PBR28 impulse response function (IRF) at 90 min produced the lowest coefficient of variation. Single-subject analysis using this IRF demonstrated microglial activation in five out of seven amyloid-positive MCI subjects. IRF parametric maps of 11 C-PBR28 uptake revealed a group-wise significant increase in neuroinflammation in amyloid-positive MCI subjects versus HC in multiple cortical association areas, and particularly in the temporal lobe. Interestingly, compartmental analysis detected group-wise increase in 11 C-PBR28 binding in the thalamus of amyloid-positive MCI subjects, while Logan parametric maps did not perform well. This study demonstrates for the first time that spectral analysis can be used to generate parametric maps of 11 C-PBR28 uptake, and is able to detect microglial activation in amyloid-positive MCI subjects. IRF parametric maps of 11 C-PBR28 uptake allow voxel-wise single-subject analysis and could be used to evaluate microglial activation in individual subjects.

Analysis of essential oils from Voacanga africana seeds at different hydrodistillation extraction stages: chemical composition, antioxidant activity and antimicrobial activity.

PubMed

Liu, Xiong; Yang, Dongliang; Liu, Jiajia; Ren, Na

2015-01-01

In this study, essential oils from Voacanga africana seeds at different extraction stages were investigated. In the chemical composition analysis, 27 compounds representing 86.69-95.03% of the total essential oils were identified and quantified. The main constituents in essential oils were terpenoids, alcohols and fatty acids accounting for 15.03-24.36%, 21.57-34.43% and 33.06-57.37%, respectively. Moreover, the analysis also revealed that essential oils from different extraction stages possessed different chemical compositions. In the antioxidant evaluation, all analysed oils showed similar antioxidant behaviours, and the concentrations of essential oils providing 50% inhibition of DPPH-scavenging activity (IC50) were about 25 mg/mL. In the antimicrobial experiments, essential oils from different extraction stages exhibited different antimicrobial activities. The antimicrobial activity of oils was affected by extraction stages. By controlling extraction stages, it is promising to obtain essential oils with desired antimicrobial activities.

The influence of emotional interference on cognitive control: A meta-analysis of neuroimaging studies using the emotional Stroop task.

PubMed

Song, Sensen; Zilverstand, Anna; Song, Hongwen; d'Oleire Uquillas, Federico; Wang, Yongming; Xie, Chao; Cheng, Li; Zou, Zhiling

2017-05-18

The neural correlates underlying the influence of emotional interference on cognitive control remain a topic of discussion. Here, we assessed 16 neuroimaging studies that used an emotional Stroop task and that reported a significant interaction effect between emotion (stimulus type) and cognitive conflict. There were a total of 330 participants, equaling 132 foci for an activation likelihood estimation (ALE) analysis. Results revealed consistent brain activation patterns related to emotionally-salient stimuli (as compared to emotionally-neutral trials) during cognitive conflict trials [incongruent trials (with task-irrelevant information interfering), versus congruent/baseline trials (less disturbance from task-irrelevant information)], that span the lateral prefrontal cortex (dorsolateral prefrontal cortex and inferior frontal gyrus), the medial prefrontal cortex, and the dorsal anterior cingulate cortex. Comparing mild emotional interference trials (without semantic conflict) versus intense emotional interference trials (with semantic conflict), revealed that while concurrent activation in similar brain regions as mentioned above was found for intense emotional interference trials, activation for mild emotional interference trials was only found in the precentral/postcentral gyrus. These data provide evidence for the potential neural mechanisms underlying emotional interference on cognitive control, and further elucidate an important distinction in brain activation patterns for different levels of emotional conflict across emotional Stroop tasks.

Simultaneous recordings from the primary visual cortex and lateral geniculate nucleus reveal rhythmic interactions and a cortical source for γ-band oscillations.

PubMed

Bastos, Andre M; Briggs, Farran; Alitto, Henry J; Mangun, George R; Usrey, W Martin

2014-05-28

Oscillatory synchronization of neuronal activity has been proposed as a mechanism to modulate effective connectivity between interacting neuronal populations. In the visual system, oscillations in the gamma-frequency range (30-100 Hz) are thought to subserve corticocortical communication. To test whether a similar mechanism might influence subcortical-cortical communication, we recorded local field potential activity from retinotopically aligned regions in the lateral geniculate nucleus (LGN) and primary visual cortex (V1) of alert macaque monkeys viewing stimuli known to produce strong cortical gamma-band oscillations. As predicted, we found robust gamma-band power in V1. In contrast, visual stimulation did not evoke gamma-band activity in the LGN. Interestingly, an analysis of oscillatory phase synchronization of LGN and V1 activity identified synchronization in the alpha (8-14 Hz) and beta (15-30 Hz) frequency bands. Further analysis of directed connectivity revealed that alpha-band interactions mediated corticogeniculate feedback processing, whereas beta-band interactions mediated geniculocortical feedforward processing. These results demonstrate that although the LGN and V1 display functional interactions in the lower frequency bands, gamma-band activity in the alert monkey is largely an emergent property of cortex. Copyright © 2014 the authors 0270-6474/14/347639-06$15.00/0.

Elimination of active tad elements during the sexual phase of the Neurospora crassa life cycle.

PubMed

Anderson, C; Tang, Q; Kinsey, J A

2001-06-01

Tad is an active LINE-like retrotransposon isolated from the Adiopodoumé strain of Neurospora crassa. Extensive analysis of other Neurospora strains has revealed no other strain with active Tad, but all strains tested have multiple copies of defective Tad elements. We have examined the ability of Tad to survive during the sexual cycle of Neurospora and find that active Tad is rapidly eliminated. The characteristics of this elimination suggest that the repeat-induced point mutation (RIP) mechanism was responsible. By the use of transformation to switch the mating type of the Adiopodoumé strain we concluded that this strain is not defective in the RIP process. Analysis of defective Tad elements isolated from a variety of strains indicates that the major difference between these elements and active Tad is due to the presence of a large number of G-C to A-T transition mutations. This would be expected if the changes were due primarily to the RIP process. Mapping of a selection of defective Tad elements reveals that they are present on all of the chromosomes; however, many of the elements are not widely shared among strains. This suggests that repeated introduction and elimination of Tad elements has occurred. Mechanisms that might be responsible for this repeated introduction are discussed. Copyright 2001 Academic Press.

EEG resolutions in detecting and decoding finger movements from spectral analysis

PubMed Central

Xiao, Ran; Ding, Lei

2015-01-01

Mu/beta rhythms are well-studied brain activities that originate from sensorimotor cortices. These rhythms reveal spectral changes in alpha and beta bands induced by movements of different body parts, e.g., hands and limbs, in electroencephalography (EEG) signals. However, less can be revealed in them about movements of different fine body parts that activate adjacent brain regions, such as individual fingers from one hand. Several studies have reported spatial and temporal couplings of rhythmic activities at different frequency bands, suggesting the existence of well-defined spectral structures across multiple frequency bands. In the present study, spectral principal component analysis (PCA) was applied on EEG data, obtained from a finger movement task, to identify cross-frequency spectral structures. Features from identified spectral structures were examined in their spatial patterns, cross-condition pattern changes, detection capability of finger movements from resting, and decoding performance of individual finger movements in comparison to classic mu/beta rhythms. These new features reveal some similar, but more different spatial and spectral patterns as compared with classic mu/beta rhythms. Decoding results further indicate that these new features (91%) can detect finger movements much better than classic mu/beta rhythms (75.6%). More importantly, these new features reveal discriminative information about movements of different fingers (fine body-part movements), which is not available in classic mu/beta rhythms. The capability in decoding fingers (and hand gestures in the future) from EEG will contribute significantly to the development of non-invasive BCI and neuroprosthesis with intuitive and flexible controls. PMID:26388720

A High-Resolution Crystal Structure of a Psychrohalophilic α–Carbonic Anhydrase from Photobacterium profundum Reveals a Unique Dimer Interface

DOE Office of Scientific and Technical Information (OSTI.GOV)

Somalinga, Vijayakumar; Buhrman, Greg; Arun, Ashikha

Bacterial α–carbonic anhydrases (α-CA) are zinc containing metalloenzymes that catalyze the rapid interconversion of CO2 to bicarbonate and a proton. We report the first crystal structure of a pyschrohalophilic α–CA from a deep-sea bacterium, Photobacterium profundum. Size exclusion chromatography of the purified P. profundum α–CA (PprCA) reveals that the protein is a heterogeneous mix of monomers and dimers. Furthermore, an “in-gel” carbonic anhydrase activity assay, also known as protonography, revealed two distinct bands corresponding to monomeric and dimeric forms of PprCA that are catalytically active. The crystal structure of PprCA was determined in its native form and reveals a highlymore » conserved “knot-topology” that is characteristic of α–CA’s. Similar to other bacterial α–CA’s, PprCA also crystallized as a dimer. Furthermore, dimer interface analysis revealed the presence of a chloride ion (Cl-) in the interface which is unique to PprCA and has not been observed in any other α–CA’s characterized so far. Molecular dynamics simulation and chloride ion occupancy analysis shows 100% occupancy for the Cl- ion in the dimer interface. Zinc coordinating triple histidine residues, substrate binding hydrophobic patch residues, and the hydrophilic proton wire residues are highly conserved in PprCA and are identical to other well-studied α–CA’s.« less

Institutional Paralysis in the Press: The Cold War in Washington State.

ERIC Educational Resources Information Center

Baldasty, Gerald J.; Winfield, Betty Houchin

1981-01-01

A content analysis of four Washington state newspapers published in 1948 reveals that they did not provide fair coverage of the House UnAmerican Activities Committee's investigation of communist infiltration at the University of Washington. (FL)

Modeling activity patterns of wildlife using time-series analysis.

PubMed

Zhang, Jindong; Hull, Vanessa; Ouyang, Zhiyun; He, Liang; Connor, Thomas; Yang, Hongbo; Huang, Jinyan; Zhou, Shiqiang; Zhang, Zejun; Zhou, Caiquan; Zhang, Hemin; Liu, Jianguo

2017-04-01

The study of wildlife activity patterns is an effective approach to understanding fundamental ecological and evolutionary processes. However, traditional statistical approaches used to conduct quantitative analysis have thus far had limited success in revealing underlying mechanisms driving activity patterns. Here, we combine wavelet analysis, a type of frequency-based time-series analysis, with high-resolution activity data from accelerometers embedded in GPS collars to explore the effects of internal states (e.g., pregnancy) and external factors (e.g., seasonal dynamics of resources and weather) on activity patterns of the endangered giant panda ( Ailuropoda melanoleuca ). Giant pandas exhibited higher frequency cycles during the winter when resources (e.g., water and forage) were relatively poor, as well as during spring, which includes the giant panda's mating season. During the summer and autumn when resources were abundant, pandas exhibited a regular activity pattern with activity peaks every 24 hr. A pregnant individual showed distinct differences in her activity pattern from other giant pandas for several months following parturition. These results indicate that animals adjust activity cycles to adapt to seasonal variation of the resources and unique physiological periods. Wavelet coherency analysis also verified the synchronization of giant panda activity level with air temperature and solar radiation at the 24-hr band. Our study also shows that wavelet analysis is an effective tool for analyzing high-resolution activity pattern data and its relationship to internal and external states, an approach that has the potential to inform wildlife conservation and management across species.

The N253F mutant structure of trehalose synthase from Deinococcus radiodurans reveals an open active-site topology.

PubMed

Chow, Sih Yao; Wang, Yung Lin; Hsieh, Yu Chiao; Lee, Guan Chiun; Liaw, Shwu Huey

2017-11-01

Trehalose synthase (TS) catalyzes the reversible conversion of maltose to trehalose and belongs to glycoside hydrolase family 13 (GH13). Previous mechanistic analysis suggested a rate-limiting protein conformational change, which is probably the opening and closing of the active site. Consistently, crystal structures of Deinococcus radiodurans TS (DrTS) in complex with the inhibitor Tris displayed an enclosed active site for catalysis of the intramoleular isomerization. In this study, the apo structure of the DrTS N253F mutant displays a new open conformation with an empty active site. Analysis of these structures suggests that substrate binding induces a domain rotation to close the active site. Such a substrate-induced domain rotation has also been observed in some other GH13 enzymes.

Analysis of serum corticosteroid-induced alkaline phosphatase isoenzyme in dogs with hepatobiliary diseases.

PubMed

Kojima, K; Ohno, K; Kanemoto, H; Goto-Koshino, Y; Fukushima, K; Tsujimoto, H

2017-05-01

To reveal the relationship between canine corticosteroid-induced alkaline phosphatase isoenzyme activity and hepatobiliary diseases. Retrospective analysis of the relationship between serum corticosteroid-induced alkaline phosphatase activity and diagnosis, serum cortisol concentration and alanine transferase activity in dogs with hepatobiliary diseases. Dogs with a history of glucocorticoid administration were excluded. Seventy-two dogs with hepatobiliary diseases were analysed. The serum corticosteroid-induced alkaline phosphatase concentration was increased in dogs with hepatobiliary diseases. There was no correlation between serum cortisol concentration and serum corticosteroid-induced alkaline phosphatase percentage or activity. Dogs with hepatobiliary disease can exhibit high serum alkaline phosphatase activity even if the dogs have not been administrated glucocorticoids and the serum cortisol concentration is normal. © 2017 British Small Animal Veterinary Association.

Assessment of an outreach program for eighth-grade science students: Measurement of affective and cognitive gains

NASA Astrophysics Data System (ADS)

Hauge, James Brian

1998-12-01

The College of Sciences and Mathematics Science Outreach Initiative was a program designed to attract students with the interest and ability to succeed in science and to keep them interested until they entered college. In this way, the Initiative sought to address the problem of a projected shortfall of scientists and engineers in the future. This study was conducted to evaluate the goals of the eighth grade component of the COSAM Initiative. These goals included: increased interest in and self-efficacy relating to science, increased achievement in science and mathematics, and increased enrollment in science and mathematics classes. Data were collected from 48 participants and 43 non-participants with surveys and from student records. Pre-treatment Chi-Square tests revealed that the groups did not differ in ethnicity, race, family income, parents' education, or parents' occupation. The surveys used were a total battery interest survey including (1) the Learning Science Things Survey (to measure interest in science topics), the Activities Interest Survey (to measure interest in science activities), the Career Orientation Survey (to measure interest in science careers) and the Learning Methods Survey (to measure interest in learning by experiential methods), (2) the Saturday Academy Survey (to measure self-efficacy concerning science activities), (3) the Saturday Academy Electronics/Eye Quiz (to test ability relating to science activities), and (4) the Summer Science Camp Survey (to measure interest in and self-efficacy concerning science activities). Student grades, SAT, and OLSAT scores, and the kinds of science and mathematics courses enrolled in during seventh and eighth grades were obtained from school records. Analysis of data using a mixed ANOVA design revealed that participation in the COSAM Initiative had no significant effect on interest in science as measured by the total battery survey. Similar analysis of Saturday Academy Survey data revealed that the participant group showed significantly greater gains in self-efficacy regarding science activities than did the non-participant group. No correlation was found between self-efficacy and ability as measured by the Electronics/Eye Quiz. Analysis of Summer Science Camp Survey data with paired samples tests revealed that interest and self-efficacy significantly increased after treatment. Interest and self-efficacy relating to Summer Science Camp activities were positively correlated after treatment. No significant effects were detected to indicate that participation in the COSAM Initiative positively affected school grades, standardized test scores, or increased the number of science and mathematics courses in which students enrolled.

Dissociation between diurnal cycles in locomotor activity, feeding behavior and hepatic PERIOD2 expression in chronic alcohol-fed mice

PubMed Central

Zhou, Peng; Werner, John H.; Lee, Donghoon; Sheppard, Aaron D.; Liangpunsakul, Suthat; Duffield, Giles E.

2015-01-01

Chronic alcohol consumption contributes to fatty liver disease. Our studies revealed that the hepatic circadian clock is disturbed in alcohol-induced hepatic steatosis, and effects of chronic alcohol administration upon the clock itself may contribute to steatosis. We extended these findings to explore the effects of chronic alcohol treatment on daily feeding and locomotor activity patterns. Mice were chronically pair-fed ad libitum for 4 weeks using the Lieber-DeCarli liquid diet, with calorie-controlled liquid and standard chow diets as control groups. Locomotor activity, feeding activity, and real-time bioluminescence recording of PERIOD2::LUCIFERASE expression in tissue explants were measured. Mice on liquid control and chow diets exhibited normal profiles of locomotor activity, with a ratio of 22:78% day/night activity and a peak during early night. This pattern was dramatically altered in alcohol-fed mice, marked by a 49:51% ratio and the absence of a distinct peak. While chow-diet fed mice had a normal 24:76% ratio of feeding activity, with a peak in the early night, this pattern was dramatically altered in both liquid-diet groups: mice had a 43:57% ratio, and an absence of a distinct peak. Temporal differences were also observed between the two liquid-diet groups during late day. Cosinor analysis revealed a ~4-h and ~6-h shift in the alcohol-fed group feeding and locomotor activity rhythms, respectively. Analysis of hepatic PER2 expression revealed that the molecular clock in alcohol-fed and control liquid-diet mice was shifted by ~11 h and ~6 h, respectively. No differences were observed in suprachiasmatic nucleus explants, suggesting that changes in circadian phase in the liver were generated independently from the central clock. These results suggest that chronic alcohol consumption and a liquid diet can differentially modulate the daily rhythmicity of locomotor and feeding behaviors, aspects that might contribute to disturbances in the circadian timing system and development of hepatic steatosis. PMID:25960184

Design, synthesis and molecular modeling of aloe-emodin derivatives as potent xanthine oxidase inhibitors.

PubMed

Shi, Da-Hua; Huang, Wei; Li, Chao; Liu, Yu-Wei; Wang, Shi-Fan

2014-03-21

A series of aloe-emodin derivatives were synthesized and evaluated as xanthine oxidase inhibitors. Among them, four aloe-emodin derivatives showed significant inhibitory activities against xanthine oxidase. The compound 4,5-dihydroxy-9,10-dioxo-9,10-dihydroanthracene-2-carbaldehyde (A1) possessed the best xanthine oxidase inhibitory activity with IC50 of 2.79 μM. Lineweaver-Burk plot analysis revealed that A1 acted as a mixed-type inhibitor for xanthine oxidase. The docking study revealed that the molecule A1 had strong interactions with the active site of xanthine oxidase and this result was in agreement with kinetic study. Consequently, compound A1 is a new-type candidate for further development for the treatment of gout. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Coagulation cascade and complement system in systemic lupus erythematosus

PubMed Central

Liang, Yan; Xie, Shang-Bo; Wu, Chang-Hao; Hu, Yuan; Zhang, Qin; Li, Si; Fan, Yin-Guang; Leng, Rui-Xue; Pan, Hai-Feng; Xiong, Hua-Bao; Ye, Dong-Qing

2018-01-01

This study was conducted to (1) characterize coagulation cascade and complement system in systemic lupus erythematosus (SLE); (2) evaluate the associations between coagulation cascade, complement system, inflammatory response and SLE disease severity; (3) test the diagnostic value of a combination of D-dimer and C4 for lupus activity. Transcriptomics, proteomics and metabolomics were performed in 24 SLE patients and 24 healthy controls. The levels of ten coagulations, seven complements and three cytokines were measured in 112 SLE patients. Clinical data were collected from 2025 SLE patients. The analysis of multi-omics data revealed the common links for the components of coagulation cascade and complement system. The results of ELISA showed coagulation cascade and complement system had an interaction effect on SLE disease severity, this effect was pronounced among patients with excess inflammation. The analysis of clinical data revealed a combination of D-dimer and C4 provided good diagnostic performance for lupus activity. This study suggested that coagulation cascade and complement system become ‘partners in crime’, contributing to SLE disease severity and identified the diagnostic value of D-dimer combined with C4for lupus activity. PMID:29599912

1,4-Naphthoquinones potently inhibiting P2X7 receptor activity.

PubMed

Faria, R X; Oliveira, F H; Salles, J P; Oliveira, A S; von Ranke, N L; Bello, M L; Rodrigues, C R; Castro, H C; Louvis, A R; Martins, D L; Ferreira, V F

2018-01-01

P2X7 receptor (P2X7R) is an ATP-gated ion-channel with potential therapeutic applications. In this study, we prepared and searched a series of 1,4-naphthoquinones derivatives to evaluate their antagonistic effect on both human and murine P2X7 receptors. We explored the structure-activity relationship and binding mode of the most active compounds using a molecular modeling approach. Biological analysis of this series (eight analogues and two compounds) revealed significant in vitro inhibition against both human and murine P2X7R. Further characterization revealed that AN-03 and AN-04 had greater potency than BBG and A740003 in inhibiting dye uptake, IL-1β release, and carrageenan-induced paw edema in vivo. Moreover, we used electrophysiology and molecular docking analysis for characterizing AN-03 and AN-04 action mechanism. These results suggest 1,4-napthoquinones, mainly AN-04, as potential leads to design new P2X7R blockers and anti-inflammatory drugs. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Revealing spatio-spectral electroencephalographic dynamics of musical mode and tempo perception by independent component analysis.

PubMed

Lin, Yuan-Pin; Duann, Jeng-Ren; Feng, Wenfeng; Chen, Jyh-Horng; Jung, Tzyy-Ping

2014-02-28

Music conveys emotion by manipulating musical structures, particularly musical mode- and tempo-impact. The neural correlates of musical mode and tempo perception revealed by electroencephalography (EEG) have not been adequately addressed in the literature. This study used independent component analysis (ICA) to systematically assess spatio-spectral EEG dynamics associated with the changes of musical mode and tempo. Empirical results showed that music with major mode augmented delta-band activity over the right sensorimotor cortex, suppressed theta activity over the superior parietal cortex, and moderately suppressed beta activity over the medial frontal cortex, compared to minor-mode music, whereas fast-tempo music engaged significant alpha suppression over the right sensorimotor cortex. The resultant EEG brain sources were comparable with previous studies obtained by other neuroimaging modalities, such as functional magnetic resonance imaging (fMRI) and positron emission tomography (PET). In conjunction with advanced dry and mobile EEG technology, the EEG results might facilitate the translation from laboratory-oriented research to real-life applications for music therapy, training and entertainment in naturalistic environments.

Metabonomics revealed xanthine oxidase-induced oxidative stress and inflammation in the pathogenesis of diabetic nephropathy.

PubMed

Liu, Jingping; Wang, Chengshi; Liu, Fang; Lu, Yanrong; Cheng, Jingqiu

2015-03-01

Diabetic nephropathy (DN) is a serious complication of diabetes mellitus (DM), which is a major public health problem in the world. To reveal the metabolic changes associated with DN, we analyzed the serum, urine, and renal extracts obtained from control and streptozotocin (STZ)-induced DN rats by (1)H NMR-based metabonomics and multivariate data analysis. A significant difference between control and DN rats was revealed in metabolic profiles, and we identified several important DN-related metabolites including increased levels of allantoin and uric acid (UA) in the DN rats, suggesting that disturbed purine metabolism may be involved in the DN. Combined with conventional histological and biological methods, we further demonstrated that xanthine oxidase (XO), a key enzyme for purine catabolism, was abnormally activated in the kidney of diabetic rats by hyperglycemia. The highly activated XO increased the level of intracellular ROS, which caused renal injury by direct oxidative damage to renal cells, and indirect inducing inflammatory responses via activating NF-κB signaling pathway. Our study highlighted that metabonomics is a promising tool to reveal the metabolic changes and the underlying mechanism involved in the pathogenesis of DN.

fMRI activation patterns in an analytic reasoning task: consistency with EEG source localization

NASA Astrophysics Data System (ADS)

Li, Bian; Vasanta, Kalyana C.; O'Boyle, Michael; Baker, Mary C.; Nutter, Brian; Mitra, Sunanda

2010-03-01

Functional magnetic resonance imaging (fMRI) is used to model brain activation patterns associated with various perceptual and cognitive processes as reflected by the hemodynamic (BOLD) response. While many sensory and motor tasks are associated with relatively simple activation patterns in localized regions, higher-order cognitive tasks may produce activity in many different brain areas involving complex neural circuitry. We applied a recently proposed probabilistic independent component analysis technique (PICA) to determine the true dimensionality of the fMRI data and used EEG localization to identify the common activated patterns (mapped as Brodmann areas) associated with a complex cognitive task like analytic reasoning. Our preliminary study suggests that a hybrid GLM/PICA analysis may reveal additional regions of activation (beyond simple GLM) that are consistent with electroencephalography (EEG) source localization patterns.

Does Hands-On Science Practices Make an Impact on Achievement in Science? A Meta-Analysis

ERIC Educational Resources Information Center

Caglak, Serdar

2017-01-01

This study aimed to investigate to what extent the use of hands-on science activities influences on students? academic achievement in science. Review of literature revealed several research studies focusing upon such aim and thus, a meta-analysis of these researches was carried out to obtain an overall effect size estimate of hands-on science…

Analysis of worldwide research in the field of cybernetics during 1997-2011.

PubMed

Singh, Virender; Perdigones, Alicia; García, José Luis; Cañas-Guerrero, Ignacio; Mazarrón, Fernando R

2014-12-01

The study provides an overview of the research activity carried out in the field of cybernetics. To do so, all research papers from 1997 to 2011 (16,445 research papers) under the category of "Computer Science, Cybernetics" of Web of Science have been processed using our in-house software which is developed specifically for this purpose. Among its multiple capabilities, this software analyses individual and compound keywords, quantifies productivity taking into account the work distribution, estimates the impact of each article and determines the collaborations established at different scales. Keywords analysis identifies the evolution of the most important research topics in the field of cybernetics and their specificity in biological aspects, as well as the research topics with lesser interest. The analysis of productivity, impact and collaborations provides a framework to assess research activity in a specific and realistic context. The geographical and institutional distribution of publications reveals the leading countries and research centres, analysing their relation to main research journals. Moreover, collaborations analysis reveals great differences in terms of internationalization and complexity of research networks. The results of this study may be very useful for the characterization and the decisions made by research in the field of cybernetics.

Isorhamnetin and Quercetin Derivatives as Anti-Acetylcholinesterase Principles of Marigold (Calendula officinalis) Flowers and Preparations

PubMed Central

Kashchenko, Nina I.; Chirikova, Nadezhda K.; Akobirshoeva, Anzurat; Zilfikarov, Ifrat N.; Vennos, Cecile

2017-01-01

Marigold (Calendula officinalis L.) is one of the most common and widespread plants used medicinally all over the world. The present study aimed to evaluate the anti-acetylcholinesterase activity of marigold flowers, detect the compounds responsible and perform chemical analysis of marigold commercial products. Analysis of 23 varieties of C. officinalis flowers introduced into Siberia allowed us to select the Greenheart Orange variety due to the superior content of flavonoids (46.87 mg/g) and the highest inhibitory activity against acetylcholinesterase (IC50 63.52 µg/mL). Flavonoids, isorhamnetin and quercetin derivatives were revealed as potential inhibitors with the application of high-performance liquid chromatography (HPLC) activity-based profiling. Investigation of the inhibitory activity of isorhamnetin glycosides demonstrated the maximal potency for isorhamnetin-3-O-(2′′,6′′-di-acetyl)-glucoside (IC50 51.26 μM) and minimal potency for typhaneoside (isorhamnetin-3-O-(2′′,6′′-di-rhamnosyl)-glucoside; IC50 94.92 µM). Among quercetin derivatives, the most active compound was quercetin-3-O-(2′′,6′′-di-acetyl)-glucoside (IC50 36.47 µM), and the least active component was manghaslin (quercetin-3-O-(2′′,6′′-di-rhamnosyl)-glucoside; IC50 94.92 µM). Some structure-activity relationships were discussed. Analysis of commercial marigold formulations revealed a reduced flavonoid content (from 7.18–19.85 mg/g) compared with introduced varieties. Liquid extract was the most enriched preparation, characterized by 3.10 mg/mL of total flavonoid content, and infusion was the least enriched formulation (0.41 mg/mL). The presented results suggest that isorhamnetin and quercetin and its glycosides can be considered as potential anti-acetylcholinesterase agents. PMID:28767066

Isorhamnetin and Quercetin Derivatives as Anti-Acetylcholinesterase Principles of Marigold (Calendula officinalis) Flowers and Preparations.

PubMed

Olennikov, Daniil N; Kashchenko, Nina I; Chirikova, Nadezhda K; Akobirshoeva, Anzurat; Zilfikarov, Ifrat N; Vennos, Cecile

2017-08-02

Marigold ( Calendula officinalis L.) is one of the most common and widespread plants used medicinally all over the world. The present study aimed to evaluate the anti-acetylcholinesterase activity of marigold flowers, detect the compounds responsible and perform chemical analysis of marigold commercial products. Analysis of 23 varieties of C. officinalis flowers introduced into Siberia allowed us to select the Greenheart Orange variety due to the superior content of flavonoids (46.87 mg/g) and the highest inhibitory activity against acetylcholinesterase (IC 50 63.52 µg/mL). Flavonoids, isorhamnetin and quercetin derivatives were revealed as potential inhibitors with the application of high-performance liquid chromatography (HPLC) activity-based profiling. Investigation of the inhibitory activity of isorhamnetin glycosides demonstrated the maximal potency for isorhamnetin-3- О -(2'',6''-di-acetyl)-glucoside (IC 50 51.26 μM) and minimal potency for typhaneoside (isorhamnetin-3- O -(2'',6''-di-rhamnosyl)-glucoside; IC 50 94.92 µM). Among quercetin derivatives, the most active compound was quercetin-3- О -(2'',6''-di-acetyl)-glucoside (IC 50 36.47 µM), and the least active component was manghaslin (quercetin-3- O -(2'',6''-di-rhamnosyl)-glucoside; IC 50 94.92 µM). Some structure-activity relationships were discussed. Analysis of commercial marigold formulations revealed a reduced flavonoid content (from 7.18-19.85 mg/g) compared with introduced varieties. Liquid extract was the most enriched preparation, characterized by 3.10 mg/mL of total flavonoid content, and infusion was the least enriched formulation (0.41 mg/mL). The presented results suggest that isorhamnetin and quercetin and its glycosides can be considered as potential anti-acetylcholinesterase agents.

Automated Video Analysis System Reveals Distinct Diurnal Behaviors in C57BL/6 and C3H/HeN Mice

PubMed Central

Adamah-Biassi, E. B.; Stepien, I.; Hudson, R.L.; Dubocovich, M.L.

2013-01-01

Advances in rodent behavior dissection using automated video recording and analysis allows detailed phenotyping. This study compared and contrasted 15 diurnal behaviors recorded continuously using an automated behavioral analysis system for a period of 14 days under a 14/10 light/dark cycle in single housed C3H/HeN (C3H) or C57BL/6 (C57) male mice. Diurnal behaviors, recorded with minimal experimental interference and analyzed using phenotypic array and temporal distribution analysis showed bimodal and unimodal profiles in the C57 and C3H mice, respectively. Phenotypic array analysis revealed distinct behavioral rhythms in activity-like behaviors (i.e. walk, hang, jump, come down) (ALB), exploration-like behaviors (i.e. dig, groom, rear up, sniff, stretch) (ELB), ingestion-like behaviors (i.e. drink, eat) (ILB) and resting-like behaviors (i.e. awake, remain low, rest, twitch) (RLB) of C3H and C57 mice. Temporal analysis demonstrated that strain and time of day affects the magnitude and distribution of the spontaneous homecage behaviors. Wheel running activity, water and food measurements correlated with timing of homecage behaviors. Subcutaneous (3 mg/kg, sc) or oral (0.02 mg/ml, oral) melatonin treatments in C57 mice did not modify either the total 24 hr magnitude or temporal distribution of homecage behaviors when compared with vehicle treatments. We conclude that C3H and C57 mice show different spontaneous activity and behavioral rhythms specifically during the night period which are not modulated by melatonin. PMID:23337734

Photogrammetric and photometric investigation of a smoke plume viewed from space.

NASA Technical Reports Server (NTRS)

Randerson, D.; Garcia, J. G.; Whitehead, V. S.

1971-01-01

Use of detailed analyses of an Apollo 6 stereographic photograph of a smoke plume which originated in southern Arizona and crossed over into Mexico to illustrate how high-resolution photography can aid meteorologists in evaluating specific air pollution events. Photogrammetric analysis of the visible smoke plume revealed that the plume was 8.06 miles long and attained a maximum width of 4000 ft, 3.0 miles from the 570-ft chimney emitting the effluent. Stereometric analysis showed that the visible top of the plume rose nearly 2400 ft above stack top, attaining 90% of this total rise 1.75 miles downwind from the source. Photometric analysis of the plume revealed a field of plume optical density that portrayed leptokurtic and bimodal distributions rather than a true Gaussian distribution. A horizontal eddy diffusivity of about 650,000 sq cm/sec and a vertical eddy diffusivity of 230,000 sq cm/sec were determined from the plume dimensions. Neutron activation analysis of plume samples revealed the elemental composition of the smoke to be copper, arsenic, selenium, indium and antimony, with trace amounts of vanadium and scandium.

Crystal structure of an avian influenza polymerase PA[subscript N] reveals an endonuclease active site

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yuan, Puwei; Bartlam, Mark; Lou, Zhiyong

2009-11-10

The heterotrimeric influenza virus polymerase, containing the PA, PB1 and PB2 proteins, catalyses viral RNA replication and transcription in the nucleus of infected cells. PB1 holds the polymerase active site and reportedly harbours endonuclease activity, whereas PB2 is responsible for cap binding. The PA amino terminus is understood to be the major functional part of the PA protein and has been implicated in several roles, including endonuclease and protease activities as well as viral RNA/complementary RNA promoter binding. Here we report the 2.2 angstrom (A) crystal structure of the N-terminal 197 residues of PA, termed PA(N), from an avian influenzamore » H5N1 virus. The PA(N) structure has an alpha/beta architecture and reveals a bound magnesium ion coordinated by a motif similar to the (P)DX(N)(D/E)XK motif characteristic of many endonucleases. Structural comparisons and mutagenesis analysis of the motif identified in PA(N) provide further evidence that PA(N) holds an endonuclease active site. Furthermore, functional analysis with in vivo ribonucleoprotein reconstitution and direct in vitro endonuclease assays strongly suggest that PA(N) holds the endonuclease active site and has critical roles in endonuclease activity of the influenza virus polymerase, rather than PB1. The high conservation of this endonuclease active site among influenza strains indicates that PA(N) is an important target for the design of new anti-influenza therapeutics.« less

The dog mite, Demodex canis: prevalence, fungal co-infection, reactions to light, and hair follicle apoptosis.

PubMed

Tsai, Yu-Jen; Chung, Wen-Cheng; Wang, Lian-Chen; Ju, Yu-Ten; Hong, Chin-Lin; Tsai, Yu-Yang; Li, Yi-Hung; Wu, Ying-Ling

2011-01-01

Infection rate, reaction to light, and hair follicle apoptosis are examined in the dogmite, Demodex canis Leydig (Prostigmata: Demodicidae), in dogs from the northern area of Taiwan. An analysis of relevant samples revealed 7.2% (73/1013) prevalence of D. canis infection. Infection during the investigation peaked each winter, with an average prevalence of 12.5% (32/255). The infection rates significantly varied in accordance with month, sex, age, and breed (p < 0.05). Most of the lesions were discovered on the backs of the infected animals, where the infection rate was 52.1% (38/73) (P < 0.05). The epidemiologic analysis of infection based on landscape area factor, found that employing a map-overlapping method showed a higher infection rate in the eastern distribution of Taiwan's northern area than other areas. Isolation tests for Microsporum canis Bodin (Onygenales: Arthrodermataceae) and Trichophyton mentagrophyte Robin (Blanchard) on the D. canis infected dogs revealed prevalence rates of 4.4% (2/45) and 2.2% (1/45), respectively. Observations demonstrated that D. canis slowly moved from a light area to a dark area. Skin samples were examined for cellular apoptosis by activated caspase3 immunohistochemical staining. Cells that surrounded the infected hair follicles were activated caspase3-positive, revealing cell apoptosis in infected follicles via the activation of caspase3.

The Dog Mite, Demodex canis: Prevalence, Fungal Co-Infection, Reactions to Light, and Hair Follicle Apoptosis

PubMed Central

Tsai, Yu-Jen; Chung, Wen-Cheng; Wang, Lian-Chen; Ju, Yu-Ten; Hong, Chin-Lin; Tsai, Yu-Yang; Li, Yi-Hung; Wu, Ying-Ling

2011-01-01

Infection rate, reaction to light, and hair follicle apoptosis are examined in the dogmite, Demodex canis Leydig (Prostigmata: Demodicidae), in dogs from the northern area of Taiwan. An analysis of relevant samples revealed 7.2% (73/1013) prevalence of D. canis infection. Infection during the investigation peaked each winter, with an average prevalence of 12.5% (32/255). The infection rates significantly varied in accordance with month, sex, age, and breed (p < 0.05). Most of the lesions were discovered on the backs of the infected animals, where the infection rate was 52.1% (38/73) (P < 0.05). The epidemiologic analysis of infection based on landscape area factor, found that employing a map-overlapping method showed a higher infection rate in the eastern distribution of Taiwan's northern area than other areas. Isolation tests for Microsporum canis Bodin (Onygenales: Arthrodermataceae) and Trichophyton mentagrophyte Robin (Blanchard) on the D. canis infected dogs revealed prevalence rates of 4.4% (2/45) and 2.2% (1/45), respectively. Observations demonstrated that D. canis slowly moved from a light area to a dark area. Skin samples were examined for cellular apoptosis by activated caspase3 immunohistochemical staining. Cells that surrounded the infected hair follicles were activated caspase3-positive, revealing cell apoptosis in infected follicles via the activation of caspase3. PMID:21867442

H3 K79 dimethylation marks developmental activation of the beta-globin gene but is reduced upon LCR-mediated high-level transcription.

PubMed

Sawado, Tomoyuki; Halow, Jessica; Im, Hogune; Ragoczy, Tobias; Bresnick, Emery H; Bender, M A; Groudine, Mark

2008-07-15

Genome-wide analyses of the relationship between H3 K79 dimethylation and transcription have revealed contradictory results. To clarify this relationship at a single locus, we analyzed expression and H3 K79 modification levels of wild-type (WT) and transcriptionally impaired beta-globin mutant genes during erythroid differentiation. Analysis of fractionated erythroid cells derived from WT/Delta locus control region (LCR) heterozygous mice reveals no significant H3 K79 dimethylation of the beta-globin gene on either allele prior to activation of transcription. Upon transcriptional activation, H3 K79 di-methylation is observed along both WT and DeltaLCR alleles, and both alleles are located in proximity to H3 K79 dimethylation nuclear foci. However, H3 K79 di-methylation is significantly increased along the DeltaLCR allele compared with the WT allele. In addition, analysis of a partial LCR deletion mutant reveals that H3 K79 dimethylation is inversely correlated with beta-globin gene expression levels. Thus, while our results support a link between H3 K79 dimethylation and gene expression, high levels of this mark are not essential for high level beta-globin gene transcription. We propose that H3 K79 dimethylation is destabilized on a highly transcribed template.

The pleiotropic effects of fisetin and hesperetin on human acute promyelocytic leukemia cells are mediated through apoptosis, cell cycle arrest, and alterations in signaling networks.

PubMed

Adan, Aysun; Baran, Yusuf

2015-11-01

Fisetin and hesperetin, flavonoids from various plants, have several pharmaceutical activities including antioxidative, anti-inflammatory, and anticancer effects. However, studies elucidating the role and the mechanism(s) of action of fisetin and hesperetin in acute promyelocytic leukemia are absent. In this study, we investigated the mechanism of the antiproliferative and apoptotic actions exerted by fisetin and hesperetin on human HL60 acute promyelocytic leukemia cells. The viability of HL60 cells was evaluated using the MTT assay, apoptosis by annexin V/propidium iodide (PI) staining and cell cycle distribution using flow cytometry, and changes in caspase-3 enzyme activity and mitochondrial transmembrane potential. Moreover, we performed whole-genome microarray gene expression analysis to reveal genes affected by fisetin and hesperetin that can be important for developing of future targeted therapy. Based on data obtained from microarray analysis, we also described biological networks modulated after fisetin and hesperetin treatment by KEGG and IPA analysis. Fisetin and hesperetin treatment showed a concentration- and time-dependent inhibition of proliferation and induced G2/M arrest for both agents and G0/G1 arrest for hesperetin at only the highest concentrations. There was a disruption of mitochondrial membrane potential together with increased caspase-3 activity. Furthermore, fisetin- and hesperetin-triggered apoptosis was confirmed by annexin V/PI analysis. The microarray gene profiling analysis revealed some important biological pathways including mitogen-activated protein kinases (MAPK) and inhibitor of DNA binding (ID) signaling pathways altered by fisetin and hesperetin treatment as well as gave a list of genes modulated ≥2-fold involved in cell proliferation, cell division, and apoptosis. Altogether, data suggested that fisetin and hesperetin have anticancer properties and deserve further investigation.

Effects of a sublethal concentration of sodium lauryl sulphate on the morphology and Na+/K+ ATPase activity in the gill of the ornate wrasse (Thalassoma pavo).

PubMed

Brunelli, Elvira; Talarico, Erminia; Corapi, Barbara; Perrotta, Ida; Tripepi, Sandro

2008-10-01

We analysed the morphology and ultrastructure of the gill apparatus of the ornate wrasse, Thalassoma pavo, under normal conditions and after exposure to a sublethal concentration of sodium lauryl sulphate (3.5 mg/l, which is one-third of the 96LC99 value). To identify the biochemical mechanisms affected by this pollutant, we evaluated and compared the localisation of Na(+)/K(+) ATPase in normal and experimental conditions. Immunocytochemical analysis revealed that this enzyme was active in the chloride cells (CCs), which were distributed in clusters in the interlamellar region of the filament. Ultrastructural analysis revealed conspicuous alterations on the epithelium after 96 and 192 h of exposure to sodium lauryl sulphate: structural features of the surface cells were lost, the appearance of intercellular lacunae changed, and cellular degeneration occurred. Statistical analysis comparing the number and dimensions of CCs in normal conditions and after 96 h of exposure showed that the CC area decreased after exposure to the detergent.

Evidence that the respiratory syncytial virus polymerase complex associates with lipid rafts in virus-infected cells: a proteomic analysis

DOE Office of Scientific and Technical Information (OSTI.GOV)

McDonald, Terence P.; Pitt, Andrew R.; Brown, Gaie

2004-12-05

The interaction between the respiratory syncytial virus (RSV) polymerase complex and lipid rafts was examined in HEp2 cells. Lipid-raft membranes were prepared from virus-infected cells and their protein content was analysed by Western blotting and mass spectrometry. This analysis revealed the presence of the N, P, L, M2-1 and M proteins. However, these proteins appeared to differ from one another in their association with these structures, with the M2-1 protein showing a greater partitioning into raft membranes compared to that of the N, P or M proteins. Determination of the polymerase activity profile of the gradient fractions revealed that 95%more » of the detectable viral enzyme activity was associated with lipid-raft membranes. Furthermore, analysis of virus-infected cells by confocal microscopy suggested an association between these proteins and the raft-lipid, GM1. Together, these results provide evidence that the RSV polymerase complex is able to associate with lipid rafts in virus-infected cells.« less

Genome sequence of Plasmopara viticola and insight into the pathogenic mechanism

PubMed Central

Yin, Ling; An, Yunhe; Qu, Junjie; Li, Xinlong; Zhang, Yali; Dry, Ian; Wu, Huijuan; Lu, Jiang

2017-01-01

Plasmopara viticola causes downy mildew disease of grapevine which is one of the most devastating diseases of viticulture worldwide. Here we report a 101.3 Mb whole genome sequence of P. viticola isolate ‘JL-7-2’ obtained by a combination of Illumina and PacBio sequencing technologies. The P. viticola genome contains 17,014 putative protein-coding genes and has ~26% repetitive sequences. A total of 1,301 putative secreted proteins, including 100 putative RXLR effectors and 90 CRN effectors were identified in this genome. In the secretome, 261 potential pathogenicity genes and 95 carbohydrate-active enzymes were predicted. Transcriptional analysis revealed that most of the RXLR effectors, pathogenicity genes and carbohydrate-active enzymes were significantly up-regulated during infection. Comparative genomic analysis revealed that P. viticola evolved independently from the Arabidopsis downy mildew pathogen Hyaloperonospora arabidopsidis. The availability of the P. viticola genome provides a valuable resource not only for comparative genomic analysis and evolutionary studies among oomycetes, but also enhance our knowledge on the mechanism of interactions between this biotrophic pathogen and its host. PMID:28417959

Biochemical and molecular analysis of an X-linked case of Leigh syndrome associated with thiamin-responsive pyruvate dehydrogenase deficiency.

PubMed

Naito, E; Ito, M; Yokota, I; Saijo, T; Matsuda, J; Osaka, H; Kimura, S; Kuroda, Y

1997-08-01

We report molecular analysis of thiamin-responsive pyruvate dehydrogenase complex (PDHC) deficiency in a patient with an X-linked form of Leigh syndrome. PDHC activity in cultured lymphoblastoid cells of this patient and his asymptomatic mother were normal in the presence of a high thiamin pyrophosphate (TPP) concentration (0.4 mmol/L). However, in the presence of a low concentration (1 x 10(-4) mmol/L) of TPP, the activity was significantly decreased, indicating that PDHC deficiency in this patient was due to decreased affinity of PDHC for TPP. The patient's older brother also was diagnosed as PDHC deficiency with Leigh syndrome, suggesting that PDHC deficiency in these two brothers was not a de novo mutation. Sequencing of the X-linked PDHC E1 alpha subunit revealed a C-->G point mutation at nucleotide 787, resulting in a substitution of glycine for arginine 263. Restriction enzyme analysis of the E1 alpha gene revealed that the mother was a heterozygote, indicating that thiamin-responsive PDHC deficiency associated with Leigh syndrome due to this mutation is transmitted by X-linked inheritance.

Variations in adolescents' motivational characteristics across gender and physical activity patterns: A latent class analysis approach.

PubMed

Lawler, Margaret; Heary, Caroline; Nixon, Elizabeth

2017-08-17

Neglecting to take account of the underlying context or type of physical activity (PA) that underpins overall involvement has resulted in a limited understanding of adolescents' PA participation. The purpose of the present research was to identify male and female adolescents' leisure time PA patterns and examine whether psychological processes derived from self-determination theory differ as a function of the pattern of PA undertaken. Nine hundred ninety-five students (61.2% females, 38.8% males; M age = 13.72 years, SD = 1.25) from eight secondary schools in Dublin, Ireland completed a physical activity recall 7 day diary and measures of intrinsic motivation, competence, relatedness, autonomy and autonomy support. Based on the diary five binary indicators of physical activity were derived reflecting recommended levels of MVPA on a minimum of 3 days, at least three sessions of non-organized physical activity (e.g. jog), team sport, individual sport, and organized non-sport physical activity (e.g. dance). Latent class analysis was used to identify subgroups of adolescents that engaged in similar patterns of physical activity. Profiles of physical activity participation were subsequently compared on motivational characteristics using Kruskal-Wallis tests. Latent class analysis revealed six distinct classes for girls (Organized Run/Swim & Dance/Gym; Organized Dance; Leisure Active Team Sport; Active Individual Sport; Walk/Run/Outdoor games; Non-Participation) and five for boys (Leisure Active Gym; Leisure Active Individual Sport; Active Team Sport; Active Mixed Type; Non-Participation). Significant differences were found between the classes. Girls characterized by participation in team or individual sport, and boys represented by team sport participation demonstrated significantly higher self-determined motivational characteristics relative to other profiles of physical activity. This research offers a nuanced insight into the underlying type of activities that constitute overall patterns of PA among adolescent boys and girls and further reveals that psychological processes vary dependent on the profile of physical activity undertaken. The findings may be useful for informing interventions aimed at promoting physical activity among young people.

Site Suitability Analysis for Beekeeping via Analythical Hyrearchy Process, Konya Example

NASA Astrophysics Data System (ADS)

Sarı, F.; Ceylan, D. A.

2017-11-01

Over the past decade, the importance of the beekeeping activities has been emphasized in the field of biodiversity, ecosystems, agriculture and human health. Thus, efficient management and deciding correct beekeeping activities seems essential to maintain and improve productivity and efficiency. Due to this importance, considering the economic contributions to the rural area, the need for suitability analysis concept has been revealed. At this point, Multi Criteria Decision Analysis (MCDA) and Geographical Information Systems (GIS) integration provides efficient solutions to the complex structure of decision- making process for beekeeping activities. In this study, site suitability analysis via Analytical Hierarchy Process (AHP) was carried out for Konya city in Turkey. Slope, elevation, aspect, distance to water resources, roads and settlements, precipitation and flora criteria are included to determine suitability. The requirements, expectations and limitations of beekeeping activities are specified with the participation of experts and stakeholders. The final suitability map were validated with existing 117 beekeeping locations and Turkish Statistical Institute 2016 beekeeping statistics for Konya province.

Establishment of gold-quartz standard GQS-1

USGS Publications Warehouse

Millard, Hugh T.; Marinenko, John; McLane, John E.

1969-01-01

A homogeneous gold-quartz standard, GQS-1, was prepared from a heterogeneous gold-bearing quartz by chemical treatment. The concentration of gold in GQS-1 was determined by both instrumental neutron activation analysis and radioisotope dilution analysis to be 2.61?0.10 parts per million. Analysis of 10 samples of the standard by both instrumental neutron activation analysis and radioisotope dilution analysis failed to reveal heterogeneity within the standard. The precision of the analytical methods, expressed as standard error, was approximately 0.1 part per million. The analytical data were also used to estimate the average size of gold particles. The chemical treatment apparently reduced the average diameter of the gold particles by at least an order of magnitude and increased the concentration of gold grains by a factor of at least 4,000.

High-resolution analysis of locomotor activity rhythms in disconnected, a visual-system mutant of Drosophila melanogaster.

PubMed

Dowse, H B; Dushay, M S; Hall, J C; Ringo, J M

1989-07-01

Free-running locomotor activity and eclosion rhythms of Drosophila melanogaster, mutant at the disconnected (disco) locus, are substantially different from the wild-type phenotype. Initial periodogram analysis revealed little or no rhythmicity (Dushay et al., 1989). We have reanalyzed the locomotor activity data using high-resolution signal analysis (maximum-entropy spectral analysis, or MESA). These analyses, corroborated by autocorrelograms, uncovered significant residual circadian rhythmicity and strong ultradian rhythms in most of the animals tested. In this regard the disco mutants are much like flies expressing mutant alleles of the period gene, as well as wild-type flies reared throughout life in constant darkness. We hypothesize that light normally triggers the coupling of multiple ultradian oscillators into a functional circadian clock and that this process is disrupted in disco flies as a result of the neural lesion.

Synthesis, pH dependent photometric and electrochemical investigation, redox mechanism and biological applications of novel Schiff base and its metallic derivatives

NASA Astrophysics Data System (ADS)

Rauf, Abdur; Shah, Afzal; Khan, Abdul Aziz; Shah, Aamir Hassan; Abbasi, Rashda; Qureshi, Irfan Zia; Ali, Saqib

2017-04-01

A novel Schiff base, 1-((2, 4-dimethylphenylimino)methyl)naphthalen-2-ol abbreviated as (HL) and its four metallic complexes were synthesized and confirmed by 1H and 13C NMR, FTIR, TGA and UV-Visible spectroscopy. Schiff base was also characterized by X-ray analysis. The photometric and electrochemical responses of all the synthesized compounds were investigated in a wide pH range. Structures of the compounds were optimized computationally for the evaluation of different physico-chemical parameters. On the basis of electrochemical results the redox mechanistic pathways of the compounds were proposed. The cytotoxicity analysis on Hela cells revealed that HL and its complexes inhibit cell growth as revealed from their IC50 values (HL):106.7 μM, (L2VO): 40.66 μM, (L2Sn): 5.92 μM, (L2Zn): 42.82 and (L2Co): 107.68 μM. The compounds were tested for anti-diabetic, triglyceride, cholesterol, anti-microbial, anti-fungal and enzyme inhibition activities. The results revealed that HL and its complexes are promising new therapeutic options as these compounds exhibit strong activity against cancer cells, diabetics, fungal and microbial inhibition.

Sensitivity of human auditory cortex to rapid frequency modulation revealed by multivariate representational similarity analysis.

PubMed

Joanisse, Marc F; DeSouza, Diedre D

2014-01-01

Functional Magnetic Resonance Imaging (fMRI) was used to investigate the extent, magnitude, and pattern of brain activity in response to rapid frequency-modulated sounds. We examined this by manipulating the direction (rise vs. fall) and the rate (fast vs. slow) of the apparent pitch of iterated rippled noise (IRN) bursts. Acoustic parameters were selected to capture features used in phoneme contrasts, however the stimuli themselves were not perceived as speech per se. Participants were scanned as they passively listened to sounds in an event-related paradigm. Univariate analyses revealed a greater level and extent of activation in bilateral auditory cortex in response to frequency-modulated sweeps compared to steady-state sounds. This effect was stronger in the left hemisphere. However, no regions showed selectivity for either rate or direction of frequency modulation. In contrast, multivoxel pattern analysis (MVPA) revealed feature-specific encoding for direction of modulation in auditory cortex bilaterally. Moreover, this effect was strongest when analyses were restricted to anatomical regions lying outside Heschl's gyrus. We found no support for feature-specific encoding of frequency modulation rate. Differential findings of modulation rate and direction of modulation are discussed with respect to their relevance to phonetic discrimination.

Pervasive competition between threat and reward in the brain

PubMed Central

Choi, Jong Moon; Padmala, Srikanth; Spechler, Philip

2014-01-01

In the current functional MRI study, we investigated interactions between reward and threat processing. Visual cues at the start of each trial informed participants about the chance of winning monetary reward and/or receiving a mild aversive shock. We tested two competing hypothesis: according to the ‘salience hypothesis’, in the condition involving both reward and threat, enhanced activation would be observed because of increased salience; according to the ‘competition hypothesis’, the processing of reward and threat would trade-off against each other, leading to reduced activation. Analysis of skin conductance data during a delay phase revealed an interaction between reward and threat processing, such that the effect of reward was reduced during threat and the effect of threat was reduced during reward. Analysis of imaging data during the same task phase revealed interactions between reward and threat processing in several regions, including the midbrain/ventral tegmental area, caudate, putamen, bed nucleus of the stria terminalis, anterior insula, middle frontal gyrus and dorsal anterior cingulate cortex. Taken together, our findings reveal conditions during which reward and threat trade-off against each other across multiple sites. Such interactions are suggestive of competitive processes and may reflect the organization of opponent systems in the brain. PMID:23547242

Proteomic analysis reveals diverse proline hydroxylation-mediated oxygen-sensing cellular pathways in cancer cells

PubMed Central

Liu, Bing; Gao, Yankun; Ruan, Hai-Bin; Chen, Yue

2016-01-01

Proline hydroxylation is a critical cellular mechanism regulating oxygen-response pathways in tumor initiation and progression. Yet, its substrate diversity and functions remain largely unknown. Here, we report a system-wide analysis to characterize proline hydroxylation substrates in cancer cells using an immunoaffinity-purification assisted proteomics strategy. We identified 562 sites from 272 proteins in HeLa cells. Bioinformatic analysis revealed that proline hydroxylation substrates are significantly enriched with mRNA processing and stress-response cellular pathways with canonical and diverse flanking sequence motifs. Structural analysis indicates a significant enrichment of proline hydroxylation participating in the secondary structure of substrate proteins. Our study identified and validated Brd4, a key transcription factor, as a novel proline hydroxylation substrate. Functional analysis showed that the inhibition of proline hydroxylation pathway significantly reduced the proline hydroxylation abundance on Brd4 and affected Brd4-mediated transcriptional activity as well as cell proliferation in AML leukemia cells. Taken together, our study identified a broad regulatory role of proline hydroxylation in cellular oxygen-sensing pathways and revealed potentially new targets that dynamically respond to hypoxia microenvironment in tumor cells. PMID:27764789

Sperm motility development in the epididymis is associated with decreased glycogen synthase kinase-3 and protein phosphatase 1 activity.

PubMed

Vijayaraghavan, S; Stephens, D T; Trautman, K; Smith, G D; Khatra, B; da Cruz e Silva, E F; Greengard, P

1996-03-01

Immotile bovine caput epididymal sperm contain levels of protein phosphatase activity twofold higher than do mature motile caudal sperm. Comparison of the inhibition profiles of endogenous phosphatase activities detected by okadaic acid (OA) and calyculin A (CA) revealed a pattern consistent with the predominance of a type 1 protein phosphatase (PP1). Immunoblot analysis identified PP1 gamma 2 (the testis-specific isoform of PP1) as the only PP1 isoform in sperm and showed little protein phosphatase 2A (PP2A). In addition, of the known PP1 inhibitors, i.e., DARPP-32, inhibitor 1 (I1), and inhibitor 2 (I2), only I2-like activity was detected in sperm. Inhibition of PP1 by the heat-stable I2-like activity purified from sperm could be reversed with purified glycogen synthase kinase-3 (GSK-3). Furthermore, sperm extracts contain an inactive complex of PP1 and I2 (termed PP1I) that could also be activated by purified GSK-3. The presence of GSK-3 in sperm was demonstrated by activation of purified PP1I, and quantitation revealed that immotile caput sperm contained sixfold higher GSK-3 activity than motile caudal sperm. Immunoblot analysis confirmed the expression of GSK-3 in sperm and revealed the occurrence of both the alpha and beta isoforms. Our findings suggest that the higher PP1 activity measured in immotile sperm, presumably due to higher GSK-3 activity, is responsible for holding motility in check. This conclusion was supported by the observation that the phosphatase inhibitors OA and CA, at micromolar and nanomolar levels, respectively, were able to induce motility in completely immotile bovine caput epididymal sperm and to stimulate the kinetic activity of mature caudal sperm. The intrasperm levels of cAMP, pH, and calcium were unaltered by treatment with these inhibitors. The results suggest a biochemical basis for the development and regulation of sperm motility and a possible physiological role for the PP1/I2/GSK-3 system.

Field trip method as an effort to reveal student environmental literacy on biodiversity issue and context

NASA Astrophysics Data System (ADS)

Rijal, M.; Saefudin; Amprasto

2018-05-01

Field trip method through investigation of local biodiversity cases can give educational experiences for students. This learning activity was efforts to reveal students environmental literacy on biodiversity. The aim of study were (1) to describe the activities of students get information about the biodiversity issue and its context through field trip, (2) to describe the students findings during field trip, and (3) to reveal students environmental literacy based on pre test and post test. The research method used weak-experiment and involved 34 participants at senior high school students in Bandung-Indonesia. The research instruments for collecting data were environmental literacy test, observation sheets and questionnaire sheets for students. The analysis of data was quantitative descriptive. The results show that more than 79% of the students gave positive view for each field trip activity, i.e students activity during work (97%-100%); students activity during gather information (79%- 100%); students activity during exchange information with friend (82%-100%); and students interested to Biodiversity after field trip activity (85%-100%). Students gain knowledge about the diversity of animal vertebrate and its characteristics, the status and condition of animals, and the source of animal with the cases of animal diversity. The students environmental literacy tends to be moderate level based on test. Meanwhile, the average of the attitudes and action greater than the components of knowledge and cognitive skills.

Cooked Food Waste-An Efficient and Less Expensive Precursor for the Generation of Activated Carbon.

PubMed

Krithiga, Thangavelu; Sabina, Xavier Janet; Rajesh, Baskaran; Ilbeygi, Hamid; Shetty, Adka Nityananda; Reddy, Ramanjaneya; Karthikeyan, Jayabalan

2018-06-01

Activated carbon was synthesized from cooked food waste, especially dehydrated rice kernels, by chemical activation method using NaOH and KOH as activating agents. It was then characterized by ultimate and proximate analysis, BET surface analysis, XRD, FTIR, Raman and SEM. The XRD patterns and Raman spectra confirmed the amorphous nature of the prepared activated carbons. Ultimate analysis showed an increase in the carbon content after activation of the raw carbon samples. Upon activation with NaOH and KOH, the surface area of the carbon sample was found to have increased from 0.3424 to 539.78 and 306.83 m2g-1 respectively. The SEM images revealed the formation of heterogeneous pores on the surface of the activated samples. The samples were then tested for their adsorption activity using acetic acid and methylene blue. Based on the regression coefficients, the adsorption kinetics of methylene blue dye were fitted with pseudo-second order model for both samples. Similarly, the Freundlich isotherm was found to be a better fit than Langmuir isotherm for both samples. The activity of thus prepared activated carbons was found to be comparable with the commercial carbon.

Vimentin is an endogenous ligand for the pattern recognition receptor Dectin-1.

PubMed

Thiagarajan, Praveena S; Yakubenko, Valentin P; Elsori, Deena H; Yadav, Satya P; Willard, Belinda; Tan, Carmela D; Rodriguez, E René; Febbraio, Maria; Cathcart, Martha K

2013-08-01

Atherosclerosis is a chronic inflammatory disorder of cholesterol deposition in monocyte-derived macrophages (MDM) within the arterial wall leading to impingement on the lumen of the vessel. In atherosclerotic lesions, MDM are the primary source of NADPH oxidase-derived superoxide anion (O₂⁻) inducing low-density lipoprotein (LDL) oxidation leading to their unregulated uptake of oxidized LDL and foam cell formation. We recently discovered that zymosan potently activates monocyte NADPH oxidase via the non-toll pattern recognition receptor (PRR), Dectin-1. Other PRRs bind endogenous human ligands, yet no such ligands have been identified for Dectin-1. Our hypothesis was that inflammation generates endogenous ligands for Dectin-1 that activate O₂⁻ production and thereby contributes to atherogenesis. Human: anti-zymosan antibodies were used to identify similar, cross-reactive epitopes in human atherosclerotic tissue extracts. Immunoblot analysis revealed consistent antibody reactive protein bands on one- and two-dimensional gel electrophoreses. Vimentin was identified by mass spectrometry in the immunoreactive bands across different tissue samples. Direct binding of vimentin to Dectin-1 was observed using BIACORE. Further data revealed that vimentin induces O₂⁻ production by human monocytes. Analysis of human atherosclerotic lesions revealed that vimentin was detected extracellularly in the necrotic core and in areas of active inflammation. Vimentin also co-localized with Dectin-1 in macrophage-rich regions where O₂⁻ is produced. We conclude that vimentin is an endogenous, activating ligand for Dectin-1. Its presence in areas of artery wall inflammation and O₂⁻ production suggests that vimentin activates Dectin-1 and contributes to the oxidation of lipids and cholesterol accumulation in atherosclerosis.

Characterization of human DHRS6, an orphan short chain dehydrogenase/reductase enzyme: a novel, cytosolic type 2 R-beta-hydroxybutyrate dehydrogenase.

PubMed

Guo, Kunde; Lukacik, Petra; Papagrigoriou, Evangelos; Meier, Marc; Lee, Wen Hwa; Adamski, Jerzy; Oppermann, Udo

2006-04-14

Human DHRS6 is a previously uncharacterized member of the short chain dehydrogenases/reductase family and displays significant homologies to bacterial hydroxybutyrate dehydrogenases. Substrate screening reveals sole NAD(+)-dependent conversion of (R)-hydroxybutyrate to acetoacetate with K(m) values of about 10 mm, consistent with plasma levels of circulating ketone bodies in situations of starvation or ketoacidosis. The structure of human DHRS6 was determined at a resolution of 1.8 A in complex with NAD(H) and reveals a tetrameric organization with a short chain dehydrogenases/reductase-typical folding pattern. A highly conserved triad of Arg residues ("triple R" motif consisting of Arg(144), Arg(188), and Arg(205)) was found to bind a sulfate molecule at the active site. Docking analysis of R-beta-hydroxybutyrate into the active site reveals an experimentally consistent model of substrate carboxylate binding and catalytically competent orientation. GFP reporter gene analysis reveals a cytosolic localization upon transfection into mammalian cells. These data establish DHRS6 as a novel, cytosolic type 2 (R)-hydroxybutyrate dehydrogenase, distinct from its well characterized mitochondrial type 1 counterpart. The properties determined for DHRS6 suggest a possible physiological role in cytosolic ketone body utilization, either as a secondary system for energy supply in starvation or to generate precursors for lipid and sterol synthesis.

Impacts of exploratory drilling for oil and gas on the benthic environment of Georges Bank

USGS Publications Warehouse

Neff, J. M.; Bothner, Michael H.; Maciolek, N. J.; Grassle, J. F.

1989-01-01

Cluster analysis revealed a strong relationship between community structure and both sediment type and water depth. Little seasonal variation was detected, but some interannual differences were revealed by cluster analysis and correspondence analysis. The replicates from a station always resembled each other more than they resembled any replicates from other stations. In addition, the combined replicates from a station always clustered with samples from that station taken on other cruises. This excellent replication and uniformity of the benthic infaunal community at a station over time made it possible to detect very subtle changes in community parameters that might be related to discharges of drilling fluid and drill cuttings. Nevertheless, no changes were detected in benthic communities of Georges Bank that could be attributed to drilling activities.

A Documentary Analysis of Abstracts Presented in European Congresses on Adapted Physical Activity.

PubMed

Sklenarikova, Jana; Kudlacek, Martin; Baloun, Ladislav; Causgrove Dunn, Janice

2016-07-01

The purpose of the study was to identify trends in research abstracts published in the books of abstracts of the European Congress of Adapted Physical Activity from 2004 to 2012. A documentary analysis of the contents of 459 abstracts was completed. Data were coded based on subcategories used in a previous study by Zhang, deLisle, and Chen (2006) and by Porretta and Sherrill (2005): number of authors, data source, sample size, type of disability, data analyses, type of study, and focus of study. Descriptive statistics calculated for each subcategory revealed an overall picture of the state and trends of scientific inquiry in adapted physical activity research in Europe.

Communication between Thiamin Cofactors in the Escherichia coli Pyruvate Dehydrogenase Complex E1 Component Active Centers EVIDENCE FOR A DIRECT PATHWAY BETWEEN THE 4′-AMINOPYRIMIDINE N1′ ATOMS

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nemeria, Natalia S; Arjunan, Palaniappa; Chandrasekhar, Krishnamoorthy

2010-11-03

Kinetic, spectroscopic, and structural analysis tested the hypothesis that a chain of residues connecting the 4{prime}-aminopyrimidine N1{prime} atoms of thiamin diphosphates (ThDPs) in the two active centers of the Escherichia coli pyruvate dehydrogenase complex E1 component provides a signal transduction pathway. Substitution of the three acidic residues (Glu{sup 571}, Glu{sup 235}, and Glu{sup 237}) and Arg{sup 606} resulted in impaired binding of the second ThDP, once the first active center was filled, suggesting a pathway for communication between the two ThDPs. (1) Steady-state kinetic and fluorescence quenching studies revealed that upon E571A, E235A, E237A, and R606A substitutions, ThDP binding inmore » the second active center was affected. (2) Analysis of the kinetics of thiazolium C2 hydrogen/deuterium exchange of enzyme-bound ThDP suggests half-of-the-sites reactivity for the E1 component, with fast (activated site) and slow exchanging sites (dormant site). The E235A and E571A variants gave no evidence for the slow exchanging site, indicating that only one of two active sites is filled with ThDP. (3) Titration of the E235A and E237A variants with methyl acetylphosphonate monitored by circular dichroism suggested that only half of the active sites were filled with a covalent predecarboxylation intermediate analog. (4) Crystal structures of E235A and E571A in complex with ThDP revealed the structural basis for the spectroscopic and kinetic observations and showed that either substitution affects cofactor binding, despite the fact that Glu{sup 235} makes no direct contact with the cofactor. The role of the conserved Glu{sup 571} residue in both catalysis and cofactor orientation is revealed by the combined results for the first time.« less

Tracking the Spatiotemporal Neural Dynamics of Real-world Object Size and Animacy in the Human Brain.

PubMed

Khaligh-Razavi, Seyed-Mahdi; Cichy, Radoslaw Martin; Pantazis, Dimitrios; Oliva, Aude

2018-06-07

Animacy and real-world size are properties that describe any object and thus bring basic order into our perception of the visual world. Here, we investigated how the human brain processes real-world size and animacy. For this, we applied representational similarity to fMRI and MEG data to yield a view of brain activity with high spatial and temporal resolutions, respectively. Analysis of fMRI data revealed that a distributed and partly overlapping set of cortical regions extending from occipital to ventral and medial temporal cortex represented animacy and real-world size. Within this set, parahippocampal cortex stood out as the region representing animacy and size stronger than most other regions. Further analysis of the detailed representational format revealed differences among regions involved in processing animacy. Analysis of MEG data revealed overlapping temporal dynamics of animacy and real-world size processing starting at around 150 msec and provided the first neuromagnetic signature of real-world object size processing. Finally, to investigate the neural dynamics of size and animacy processing simultaneously in space and time, we combined MEG and fMRI with a novel extension of MEG-fMRI fusion by representational similarity. This analysis revealed partly overlapping and distributed spatiotemporal dynamics, with parahippocampal cortex singled out as a region that represented size and animacy persistently when other regions did not. Furthermore, the analysis highlighted the role of early visual cortex in representing real-world size. A control analysis revealed that the neural dynamics of processing animacy and size were distinct from the neural dynamics of processing low-level visual features. Together, our results provide a detailed spatiotemporal view of animacy and size processing in the human brain.

Comprehensive assay of kinase catalytic activity reveals features of kinase inhibitor selectivity

PubMed Central

Anastassiadis, Theonie; Deacon, Sean W.; Devarajan, Karthik; Ma, Haiching; Peterson, Jeffrey R.

2011-01-01

Small-molecule protein kinase inhibitors are central tools for elucidating cellular signaling pathways and are promising therapeutic agents. Due to evolutionary conservation of the ATP-binding site, most kinase inhibitors that target this site promiscuously inhibit multiple kinases. Interpretation of experiments utilizing these compounds is confounded by a lack of data on the comprehensive kinase selectivity of most inhibitors. Here we profiled the activity of 178 commercially available kinase inhibitors against a panel of 300 recombinant protein kinases using a functional assay. Quantitative analysis revealed complex and often unexpected kinase-inhibitor interactions, with a wide spectrum of promiscuity. Many off-target interactions occur with seemingly unrelated kinases, revealing how large-scale profiling can be used to identify multi-targeted inhibitors of specific, diverse kinases. The results have significant implications for drug development and provide a resource for selecting compounds to elucidate kinase function and for interpreting the results of experiments that use them. PMID:22037377

Person-Centered, Physical Activity for Patients with Low Back Pain: Piloting Service Delivery

PubMed Central

Bloxham, Saul; Barter, Phil; Scragg, Slafka; Peers, Charles; Jane, Ben; Layden, Joe

2016-01-01

Low back pain (LBP) is one of the most common and costly conditions in industrialized countries. Exercise therapy has been used to treat LBP, although typically using only one mode of exercise. This paper describes the method and initial findings of a person-centered, group physical activity programme which featured as part of a multidisciplinary approach to treating LBP. Six participants (aged 50.7 ± 17 years) completed a six-week physical activity programme lasting two hours per week. A multicomponent approach to physical activity was adopted which included aerobic fitness, core activation, muscular strength and endurance, Nordic Walking, flexibility and exercise gaming. In addition, participants were required to use diary sheets to record physical activity completed at home. Results revealed significant (p < 0.05) improvements in back strength (23%), aerobic fitness (23%), negative wellbeing (32%) and disability (16%). Person’s Correlation Coefficient analysis revealed significant (p < 0.05) relationships between improvement in perceived pain and aerobic fitness (r = 0.93). It was concluded that a person-centered, multicomponent approach to physical activity may be optimal for supporting patients who self-manage LBP. PMID:27417616

Altered spontaneous brain activity in adolescent boys with pure conduct disorder revealed by regional homogeneity analysis.

PubMed

Wu, Qiong; Zhang, Xiaocui; Dong, Daifeng; Wang, Xiang; Yao, Shuqiao

2017-07-01

Functional magnetic resonance imaging (fMRI) studies have revealed abnormal neural activity in several brain regions of adolescents with conduct disorder (CD) performing various tasks. However, little is known about the spontaneous neural activity in people with CD in a resting state. The aims of this study were to investigate CD-associated regional activity abnormalities and to explore the relationship between behavioral impulsivity and regional activity abnormalities. Resting-state fMRI (rs-fMRI) scans were administered to 28 adolescents with CD and 28 age-, gender-, and IQ-matched healthy controls (HCs). The rs-fMRI data were subjected to regional homogeneity (ReHo) analysis. ReHo can demonstrate the temporal synchrony of regional blood oxygen level-dependent signals and reflect the coordination of local neuronal activity facilitating similar goals or representations. Compared to HCs, the CD group showed increased ReHo bilaterally in the insula as well as decreased ReHo in the right inferior parietal lobule, right middle temporal gyrus and right fusiform gyrus, left anterior cerebellum anterior, and right posterior cerebellum. In the CD group, mean ReHo values in the left and the right insula correlated positively with Barratt Impulsivity Scale (BIS) total scores. The results suggest that CD is associated with abnormal intrinsic brain activity, mainly in the cerebellum and temporal-parietal-limbic cortices, regions that are related to emotional and cognitive processing. BIS scores in adolescents with CD may reflect severity of abnormal neuronal synchronization in the insula.

Rational design and validation of a vanilloid-sensitive TRPV2 ion channel

PubMed Central

Yang, Fan; Vu, Simon; Yarov-Yarovoy, Vladimir; Zheng, Jie

2016-01-01

Vanilloids activation of TRPV1 represents an excellent model system of ligand-gated ion channels. Recent studies using cryo-electron microcopy (cryo-EM), computational analysis, and functional quantification revealed the location of capsaicin-binding site and critical residues mediating ligand-binding and channel activation. Based on these new findings, here we have successfully introduced high-affinity binding of capsaicin and resiniferatoxin to the vanilloid-insensitive TRPV2 channel, using a rationally designed minimal set of four point mutations (F467S–S498F–L505T–Q525E, termed TRPV2_Quad). We found that binding of resiniferatoxin activates TRPV2_Quad but the ligand-induced open state is relatively unstable, whereas binding of capsaicin to TRPV2_Quad antagonizes resiniferatoxin-induced activation likely through competition for the same binding sites. Using Rosetta-based molecular docking, we observed a common structural mechanism underlying vanilloids activation of TRPV1 and TRPV2_Quad, where the ligand serves as molecular “glue” that bridges the S4–S5 linker to the S1–S4 domain to open these channels. Our analysis revealed that capsaicin failed to activate TRPV2_Quad likely due to structural constraints preventing such bridge formation. These results not only validate our current working model for capsaicin activation of TRPV1 but also should help guide the design of drug candidate compounds for this important pain sensor. PMID:27298359

"Spacecraft Reveals Recent Geological Activity on the Moon": Exploring the Features of NASA Twitter Posts and Their Potential to Engage Adolescents

ERIC Educational Resources Information Center

Lesley, Mellinee

2014-01-01

Through a content analysis of 200 "tweets," this study was an exploration into the distinct features of text posted to NASA's "Twitter" site and the potential for these posts to serve as more engaging scientific text than traditional textbooks for adolescents. Results of the content analysis indicated the tweets and linked…

Twitter as a Potential Disaster Risk Reduction Tool. Part II: Descriptive Analysis of Identified Twitter Activity during the 2013 Hattiesburg F4 Tornado.

PubMed

Cooper, Guy Paul; Yeager, Violet; Burkle, Frederick M; Subbarao, Italo

2015-06-29

This article describes a novel triangulation methodological approach for identifying twitter activity of regional active twitter users during the 2013 Hattiesburg EF-4 Tornado. A data extraction and geographically centered filtration approach was utilized to generate Twitter data for 48 hrs pre- and post-Tornado. The data was further validated using six sigma approach utilizing GPS data. The regional analysis revealed a total of 81,441 tweets, 10,646 Twitter users, 27,309 retweets and 2637 tweets with GPS coordinates. Twitter tweet activity increased 5 fold during the response to the Hattiesburg Tornado.  Retweeting activity increased 2.2 fold. Tweets with a hashtag increased 1.4 fold. Twitter was an effective disaster risk reduction tool for the Hattiesburg EF-4 Tornado 2013.

Inhibitory effect of apocarotenoids on the activity of tyrosinase: Multi-spectroscopic and docking studies.

PubMed

Anantharaman, Amrita; Hemachandran, Hridya; Priya, Rajendra Rao; Sankari, Mohan; Gopalakrishnan, Mohan; Palanisami, Nallasamy; Siva, Ramamoorthy

2016-01-01

In this present study, the inhibitory mechanism of three selected apocarotenoids (bixin, norbixin and crocin) on the diphenolase activity of tyrosinase has been investigated. The preliminary screening results indicated that apocarotenoids inhibited tyrosinase activity in a dose-dependent manner. Kinetic analysis revealed that apocarotenoids reversibly inhibited tyrosinase activity. Analysis of fluorescence spectra showed that apocarotenoids quenched the intrinsic fluorescence intensity of the tyrosinase. Further, molecular docking results implied that apocarotenoids were allosterically bound to tyrosinase through hydrophobic interactions. The results of the in vitro studies suggested that higher concentrations of bixin and norbixin inhibited tyrosinase activity in B16F0 melanoma cells. Our results suggested that apocarotenoids could form the basis for the design of novel tyrosinase inhibitors. Copyright © 2015 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

Inhibition of RAS activation due to a homozygous ezrin variant in patients with profound intellectual disability.

PubMed

Riecken, Lars Björn; Tawamie, Hasan; Dornblut, Carsten; Buchert, Rebecca; Ismayel, Amina; Schulz, Alexander; Schumacher, Johannes; Sticht, Heinrich; Pohl, Katja J; Cui, Yan; Reis, André; Morrison, Helen; Abou Jamra, Rami

2015-02-01

Gain-of-function alterations in several components and modulators of the Ras-MAPK pathway lead to dysregulation of the pathway and cause a broad spectrum of autosomal dominant developmental disorders, collectively known as RASopathies. These findings demonstrate the importance of tight multilevel Ras regulation to safeguard signaling output and prevent aberrant activity. We have recently identified ezrin as a novel regulatory element required for Ras activation. Homozygosity mapping and exome sequencing have now revealed the first presumably disease-causing variant in the coding gene EZR in two siblings with a profound intellectual disability. Localization and membrane targeting of the altered ezrin protein appeared normal but molecular modeling suggested protein interaction surfaces to be disturbed. Functional analysis revealed that the altered ezrin protein is no longer able to bind Ras and facilitate its activation. Furthermore, expression of the altered ezrin protein in different cell lines resulted in abnormal cellular processes, including reduced proliferation and neuritogenesis, thus revealing a possible mechanism for its phenotype in humans. To our knowledge, this is the first report of an autosomal recessively inherited loss-of-function mutation causing reduced Ras activity and thus extends and complements the pathogenicity spectrum of known Ras-MAPK pathway disturbances. © 2014 WILEY PERIODICALS, INC.

Immobilization-associated osteoporosis in primates

NASA Technical Reports Server (NTRS)

Young, D. R.; Niklowitz, W. J.; Brown, R. J.; Jee, W. S. S.

1986-01-01

Osteopenic changes in the tibial compact bone of fifteen adult male monkeys immobilized for up to 7 months are examined histologically. Osteonal formation in the proximal tibia is analyzed. The analysis reveals the loss of haversian bone in the proximal tibia, increased activation with excessive depth of penetration of osteoclastic activity, rapid bone loss, and resorption cavities of irregular size and orientation. Osteonal formation following reambulation is examined; the recovery of cortical is a repair and rejuvenation process characterized by refilling of resorption cavities and remodeling activities.

A comprehensive functional analysis of PTEN mutations: implications in tumor- and autism-related syndromes.

PubMed

Rodríguez-Escudero, Isabel; Oliver, María D; Andrés-Pons, Amparo; Molina, María; Cid, Víctor J; Pulido, Rafael

2011-11-01

The PTEN (phosphatase and tensin homolog) phosphatase is unique in mammals in terms of its tumor suppressor activity, exerted by dephosphorylation of the lipid second messenger PIP(3) (phosphatidylinositol 3,4,5-trisphosphate), which activates the phosphoinositide 3-kinase/Akt/mTOR (mammalian target of rapamycin) oncogenic pathway. Loss-of-function mutations in the PTEN gene are frequent in human cancer and in the germline of patients with PTEN hamartoma tumor-related syndromes (PHTSs). In addition, PTEN is mutated in patients with autism spectrum disorders (ASDs), although no functional information on these mutations is available. Here, we report a comprehensive in vivo functional analysis of human PTEN using a heterologous yeast reconstitution system. Ala-scanning mutagenesis at the catalytic loops of PTEN outlined the critical role of residues within the P-catalytic loop for PIP(3) phosphatase activity in vivo. PTEN mutations that mimic the P-catalytic loop of mammalian PTEN-like proteins (TPTE, TPIP, tensins and auxilins) affected PTEN function variably, whereas tumor- or PHTS-associated mutations targeting the PTEN P-loop produced complete loss of function. Conversely, Ala-substitutions, as well as tumor-related mutations at the WPD- and TI-catalytic loops, displayed partial activity in many cases. Interestingly, a tumor-related D92N mutation was partially active, supporting the notion that the PTEN Asp92 residue might not function as the catalytic general acid. The analysis of a panel of ASD-associated hereditary PTEN mutations revealed that most of them did not substantially abrogate PTEN activity in vivo, whereas most of PHTS-associated mutations did. Our findings reveal distinctive functional patterns among PTEN mutations found in tumors and in the germline of PHTS and ASD patients, which could be relevant for therapy.

Integrated analysis reveals that STAT3 is central to the crosstalk between HER/ErbB receptor signaling pathways in human mammary epithelial cells

DOE PAGES

Gong, Chunhong; Zhang, Yi; Shankaran, Harish; ...

2014-10-02

Human epidermal growth factor receptors (HER, also known as ErbB) drive cellular proliferation, pro-survival and stress responses by activating several downstream kinases, in particular ERK, p38, JNK (SAPK), the PI3K/AKT, as well as various transcriptional regulators such as STAT3. When co-expressed, first three members of HER family (HER1-3) can form homo- and hetero-dimers. Based on the considerable evidence which suggest that every receptor dimer activates intracellular signaling pathways differentially, we hypothesized that the HER dimerization pattern is a better predictor of downstream signaling than the total receptor activation levels. We validated our hypothesis using a combination of model-based analysis tomore » quantify the HER dimerization patterns and multi-factorial experiments where HER dimerization patterns and signaling crosstalk were rationally perturbed. We have measured the activation of HER1-3 receptors and of the sentinel signaling proteins ERK, AKT, p38, JNK, STAT3 as a function of time in a panel of human mammary epithelial (HME) cells expressing different levels of HER1-3 stimulated with various ligand combinations. Our analysis using multiple ways of clustering the activation data has confirmed that the HER receptor dimer is a better predictor of the signaling through p38, ERK and AKT pathways than the total HER receptor expression and activation levels. Targeted inhibition studies to identify the causal effects allowed us to obtain a consensus regulatory interaction model, which revealed that STAT3 occupies a central role in the crosstalk between the studied pathways.« less

Comprehensive analysis of transcriptome response to salinity stress in the halophytic turf grass Sporobolus virginicus

PubMed Central

Yamamoto, Naoki; Takano, Tomoyuki; Tanaka, Keisuke; Ishige, Taichiro; Terashima, Shin; Endo, Chisato; Kurusu, Takamitsu; Yajima, Shunsuke; Yano, Kentaro; Tada, Yuichi

2015-01-01

The turf grass Sporobolus virginicus is halophyte and has high salinity tolerance. To investigate the molecular basis of its remarkable tolerance, we performed Illumina high-throughput RNA sequencing on roots and shoots of a S. virginicus genotype under normal and saline conditions. The 130 million short reads were assembled into 444,242 unigenes. A comparative analysis of the transcriptome with rice and Arabidopsis transcriptome revealed six turf grass-specific unigenes encoding transcription factors. Interestingly, all of them showed root specific expression and five of them encode bZIP type transcription factors. Another remarkable transcriptional feature of S. virginicus was activation of specific pathways under salinity stress. Pathway enrichment analysis suggested transcriptional activation of amino acid, pyruvate, and phospholipid metabolism. Up-regulation of several unigenes, previously shown to respond to salt stress in other halophytes was also observed. Gene Ontology enrichment analysis revealed that unigenes assigned as proteins in response to water stress, such as dehydrin and aquaporin, and transporters such as cation, amino acid, and citrate transporters, and H+-ATPase, were up-regulated in both shoots and roots under salinity. A correspondence analysis of the enriched pathways in turf grass cells, but not in rice cells, revealed two groups of unigenes similarly up-regulated in the turf grass in response to salt stress; one of the groups, showing excessive up-regulation under salinity, included unigenes homologos to salinity responsive genes in other halophytes. Thus, the present study identified candidate genes involved in salt tolerance of S. virginicus. This genetic resource should be valuable for understanding the mechanisms underlying high salt tolerance in S. virginicus. This information can also provide insight into salt tolerance in other halophytes. PMID:25954282

Hydrocortisone activation of human herpesvirus 8 viral DNA replication and gene expression in vitro.

PubMed

Hudnall, S D; Rady, P L; Tyring, S K; Fish, J C

1999-03-15

Patients undergoing chronic steroid therapy for organ transplantation are at increased risk for development of human herpes virus 8(HHV-8)-associated Kaposi's sarcoma (KS). It has also been reported that following steroid withdrawal, KS lesions often undergo partial or complete regression. We have examined the effect of corticosteroid treatment on HHV-8 replication, gene expression, and lytic protein expression in BCBL-1 cells in vitro. BCBL-1 cells were collected after culture for 24-72 hr with hydrocortisone (HC) 1-5 microM, phorbol ester 20 ng/ml (positive control), and culture medium only (negative control). HHV-8 genomic conformation was examined by Gardella gel analysis. mRNA expression of viral cyclin (v-Cyc), viral Bcl-2 (v-Bcl-2), viral macrophage inflammatory protein-I (v-MIP-I), viral interferon regulatory factor-1(v-IRF-1), and viral tegument protein (TP) was examined by RT-PCR Southern blot. Viral protein expression within the cells was examined by indirect immunofluorescence using 5 different HHV-8 positive antisera from 4 renal transplant recipients and 1 patient with classic KS. Gardella gel analysis revealed that HC induced an accumulation of the linear replicative genomic form of the virus in a time-dependent fashion. Southern blot analysis of the RT-PCR products revealed that HC induced increased expression of v-IRF-1, v-Bcl-2, and TP mRNA, with little discernible effect on v-Cyc, and v-MIP-I. Immunofluorescence revealed that HC induced increased numbers of cells expressing lytic antigens. These data indicate that hydrocortisone acts directly on BCBL-1 cells to activate the lytic cycle of HHV-8 and provide further support for the hypothesis that HHV-8 is activated in corticosteroid-treated immunocompromised patients.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sobinoff, A.P.; Pye, V.; Nixon, B.

Benzo(a)pyrene (BaP) is an ovotoxic constituent of cigarette smoke associated with pre-mature ovarian failure and decreased rates of conception in IVF patients. Although the overall effect of BaP on female fertility has been documented, the exact molecular mechanisms behind its ovotoxicity remain elusive. In this study we examined the effects of BaP exposure on the ovarian transcriptome, and observed the effects of in vivo exposure on oocyte dysfunction. Microarray analysis of BaP cultured neonatal ovaries revealed a complex mechanism of ovotoxicity involving a small cohort of genes associated with follicular growth, cell cycle progression, and cell death. Histomorphological and immunohistochemicalmore » analysis supported these results, with BaP exposure causing increased primordial follicle activation and developing follicle atresia in vitro and in vivo. Functional analysis of oocytes obtained from adult Swiss mice treated neonatally revealed significantly increased levels of mitochondrial ROS/lipid peroxidation, and severely reduced sperm-egg binding and fusion in both low (1.5 mg/kg/daily) and high (3 mg/kg/daily) dose treatments. Our results reveal a complex mechanism of BaP induced ovotoxicity involving developing follicle atresia and accelerated primordial follicle activation, and suggest short term neonatal BaP exposure causes mitochondrial leakage resulting in reduced oolemma fluidity and impaired fertilisation in adulthood. This study highlights BaP as a key compound which may be partially responsible for the documented effects of cigarette smoke on follicular development and sub-fertility. -- Highlights: ► BaP exposure up-regulates canonical pathways linked with follicular growth/atresia. ► BaP causes primordial follicle activation and developing follicle atresia. ► BaP causes oocyte mitochondrial ROS and lipid peroxidation, impairing fertilisation. ► Short term neonatal BaP exposure compromises adult oocyte quality.« less

Manganese- and 1-methyl-4-phenylpyridinium-induced neurotoxicity display differences in morphological, electrophysiological and genome-wide alterations: implications for idiopathic Parkinson's disease.

PubMed

Mythri, Rajeswara Babu; Raghunath, Narayana Reddy; Narwade, Santosh Chandrakant; Pandareesh, Mirazkar Dasharatha Rao; Sabitha, Kollarkandi Rajesh; Aiyaz, Mohamad; Chand, Bipin; Sule, Manas; Ghosh, Krittika; Kumar, Senthil; Shankarappa, Bhagyalakshmi; Soundararajan, Soundarya; Alladi, Phalguni Anand; Purushottam, Meera; Gayathri, Narayanappa; Deobagkar, Deepti Dileep; Laxmi, Thenkanidiyoor Rao; Srinivas Bharath, Muchukunte Mukunda

2017-11-01

Idiopathic Parkinson's disease and manganese-induced atypical parkinsonism are characterized by movement disorder and nigrostriatal pathology. Although clinical features, brain region involved and responsiveness to levodopa distinguish both, differences at the neuronal level are largely unknown. We studied the morphological, neurophysiological and molecular differences in dopaminergic neurons exposed to the Parkinson's disease toxin 1-methyl-4-phenylpyridinium ion (MPP + ) and manganese (Mn), followed by validation in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine and Mn mouse models. Morphological analysis highlighted loss of neuronal processes in the MPP + and not the Mn model. Cellular network dynamics of dopaminergic neurons characterized by spike frequency and inter-spike intervals indicated major neuronal population (~ 93%) with slow discharge rates (0-5 Hz). While MPP + exposure suppressed the firing of these neurons, Mn neither suppressed nor elevated the neuronal activity. High-throughput transcriptomic analysis revealed up-regulation of 694 and 603 genes and down-regulation of 428 and 255 genes in the MPP + and Mn models respectively. Many differentially expressed genes were unique to either models and contributed to neuroinflammation, metabolic/mitochondrial function, apoptosis and nuclear function, synaptic plasticity, neurotransmission and cytoskeleton. Analysis of the Janus kinase-signal transducer and activator of transcription pathway with implications for neuritogenesis and neuronal proliferation revealed contrasting profile in both models. Genome-wide DNA methylomics revealed differences between both models and substantiated the epigenetic basis of the difference in the Janus kinase-signal transducer and activator of transcription pathway. We conclude that idiopathic Parkinson's disease and atypical parkinsonism have divergent neurotoxicological manifestation at the dopaminergic neuronal level with implications for pathobiology and evolution of novel therapeutics. Cover Image for this issue: doi. 10.1111/jnc.13821. © 2017 International Society for Neurochemistry.

Data Mining Methods for Omics and Knowledge of Crude Medicinal Plants toward Big Data Biology

PubMed Central

Afendi, Farit M.; Ono, Naoaki; Nakamura, Yukiko; Nakamura, Kensuke; Darusman, Latifah K.; Kibinge, Nelson; Morita, Aki Hirai; Tanaka, Ken; Horai, Hisayuki; Altaf-Ul-Amin, Md.; Kanaya, Shigehiko

2013-01-01

Molecular biological data has rapidly increased with the recent progress of the Omics fields, e.g., genomics, transcriptomics, proteomics and metabolomics that necessitates the development of databases and methods for efficient storage, retrieval, integration and analysis of massive data. The present study reviews the usage of KNApSAcK Family DB in metabolomics and related area, discusses several statistical methods for handling multivariate data and shows their application on Indonesian blended herbal medicines (Jamu) as a case study. Exploration using Biplot reveals many plants are rarely utilized while some plants are highly utilized toward specific efficacy. Furthermore, the ingredients of Jamu formulas are modeled using Partial Least Squares Discriminant Analysis (PLS-DA) in order to predict their efficacy. The plants used in each Jamu medicine served as the predictors, whereas the efficacy of each Jamu provided the responses. This model produces 71.6% correct classification in predicting efficacy. Permutation test then is used to determine plants that serve as main ingredients in Jamu formula by evaluating the significance of the PLS-DA coefficients. Next, in order to explain the role of plants that serve as main ingredients in Jamu medicines, information of pharmacological activity of the plants is added to the predictor block. Then N-PLS-DA model, multiway version of PLS-DA, is utilized to handle the three-dimensional array of the predictor block. The resulting N-PLS-DA model reveals that the effects of some pharmacological activities are specific for certain efficacy and the other activities are diverse toward many efficacies. Mathematical modeling introduced in the present study can be utilized in global analysis of big data targeting to reveal the underlying biology. PMID:24688691

Integrated Genomic Characterization Reveals Novel, Therapeutically Relevant Drug Targets in FGFR and EGFR Pathways in Sporadic Intrahepatic Cholangiocarcinoma

PubMed Central

Liang, Winnie S.; Fonseca, Rafael; Bryce, Alan H.; McCullough, Ann E.; Barrett, Michael T.; Hunt, Katherine; Patel, Maitray D.; Young, Scott W.; Collins, Joseph M.; Silva, Alvin C.; Condjella, Rachel M.; Block, Matthew; McWilliams, Robert R.; Lazaridis, Konstantinos N.; Klee, Eric W.; Bible, Keith C.; Harris, Pamela; Oliver, Gavin R.; Bhavsar, Jaysheel D.; Nair, Asha A.; Middha, Sumit; Asmann, Yan; Kocher, Jean-Pierre; Schahl, Kimberly; Kipp, Benjamin R.; Barr Fritcher, Emily G.; Baker, Angela; Aldrich, Jessica; Kurdoglu, Ahmet; Izatt, Tyler; Christoforides, Alexis; Cherni, Irene; Nasser, Sara; Reiman, Rebecca; Phillips, Lori; McDonald, Jackie; Adkins, Jonathan; Mastrian, Stephen D.; Placek, Pamela; Watanabe, Aprill T.; LoBello, Janine; Han, Haiyong; Von Hoff, Daniel; Craig, David W.; Stewart, A. Keith; Carpten, John D.

2014-01-01

Advanced cholangiocarcinoma continues to harbor a difficult prognosis and therapeutic options have been limited. During the course of a clinical trial of whole genomic sequencing seeking druggable targets, we examined six patients with advanced cholangiocarcinoma. Integrated genome-wide and whole transcriptome sequence analyses were performed on tumors from six patients with advanced, sporadic intrahepatic cholangiocarcinoma (SIC) to identify potential therapeutically actionable events. Among the somatic events captured in our analysis, we uncovered two novel therapeutically relevant genomic contexts that when acted upon, resulted in preliminary evidence of anti-tumor activity. Genome-wide structural analysis of sequence data revealed recurrent translocation events involving the FGFR2 locus in three of six assessed patients. These observations and supporting evidence triggered the use of FGFR inhibitors in these patients. In one example, preliminary anti-tumor activity of pazopanib (in vitro FGFR2 IC50≈350 nM) was noted in a patient with an FGFR2-TACC3 fusion. After progression on pazopanib, the same patient also had stable disease on ponatinib, a pan-FGFR inhibitor (in vitro, FGFR2 IC50≈8 nM). In an independent non-FGFR2 translocation patient, exome and transcriptome analysis revealed an allele specific somatic nonsense mutation (E384X) in ERRFI1, a direct negative regulator of EGFR activation. Rapid and robust disease regression was noted in this ERRFI1 inactivated tumor when treated with erlotinib, an EGFR kinase inhibitor. FGFR2 fusions and ERRFI mutations may represent novel targets in sporadic intrahepatic cholangiocarcinoma and trials should be characterized in larger cohorts of patients with these aberrations. PMID:24550739

Analysis of SOS-Induced Spontaneous Prophage Induction in Corynebacterium glutamicum at the Single-Cell Level

PubMed Central

Nanda, Arun M.; Heyer, Antonia; Krämer, Christina; Grünberger, Alexander; Kohlheyer, Dietrich

2014-01-01

The genome of the Gram-positive soil bacterium Corynebacterium glutamicum ATCC 13032 contains three integrated prophage elements (CGP1 to -3). Recently, it was shown that the large lysogenic prophage CGP3 (∼187 kbp) is excised spontaneously in a small number of cells. In this study, we provide evidence that a spontaneously induced SOS response is partly responsible for the observed spontaneous CGP3 induction. Whereas previous studies focused mainly on the induction of prophages at the population level, we analyzed the spontaneous CGP3 induction at the single-cell level using promoters of phage genes (Pint2 and Plysin) fused to reporter genes encoding fluorescent proteins. Flow-cytometric analysis revealed a spontaneous CGP3 activity in about 0.01 to 0.08% of the cells grown in standard minimal medium, which displayed a significantly reduced viability. A PrecA-eyfp promoter fusion revealed that a small fraction of C. glutamicum cells (∼0.2%) exhibited a spontaneous induction of the SOS response. Correlation of PrecA to the activity of downstream SOS genes (PdivS and PrecN) confirmed a bona fide induction of this stress response rather than stochastic gene expression. Interestingly, the reporter output of PrecA and CGP3 promoter fusions displayed a positive correlation at the single-cell level (ρ = 0.44 to 0.77). Furthermore, analysis of the PrecA-eyfp/Pint2-e2-crimson strain during growth revealed the highest percentage of spontaneous PrecA and Pint2 activity in the early exponential phase, when fast replication occurs. Based on these studies, we postulate that spontaneously occurring DNA damage induces the SOS response, which in turn triggers the induction of lysogenic prophages. PMID:24163339

Within-subject joint independent component analysis of simultaneous fMRI/ERP in an auditory oddball paradigm

PubMed Central

MANGALATHU-ARUMANA, J.; BEARDSLEY, S. A.; LIEBENTHAL, E.

2012-01-01

The integration of event-related potential (ERP) and functional magnetic resonance imaging (fMRI) can contribute to characterizing neural networks with high temporal and spatial resolution. This research aimed to determine the sensitivity and limitations of applying joint independent component analysis (jICA) within-subjects, for ERP and fMRI data collected simultaneously in a parametric auditory frequency oddball paradigm. In a group of 20 subjects, an increase in ERP peak amplitude ranging 1–8 μV in the time window of the P300 (350–700ms), and a correlated increase in fMRI signal in a network of regions including the right superior temporal and supramarginal gyri, was observed with the increase in deviant frequency difference. JICA of the same ERP and fMRI group data revealed activity in a similar network, albeit with stronger amplitude and larger extent. In addition, activity in the left pre- and post- central gyri, likely associated with right hand somato-motor response, was observed only with the jICA approach. Within-subject, the jICA approach revealed significantly stronger and more extensive activity in the brain regions associated with the auditory P300 than the P300 linear regression analysis. The results suggest that with the incorporation of spatial and temporal information from both imaging modalities, jICA may be a more sensitive method for extracting common sources of activity between ERP and fMRI. PMID:22377443

A new dust source map of Central Asia derived from MODIS Terra/Aqua data using dust enhancement techniques

NASA Astrophysics Data System (ADS)

Nobakht, Mohamad; Shahgedanova, Maria; White, Kevin

2017-04-01

Central Asian deserts are a significant source of dust in the middle latitudes, where economic activity and health of millions of people are affected by dust storms. Detailed knowledge of sources of dust, controls over their activity, seasonality and atmospheric pathways are of crucial importance but to date, these data are limited. This paper presents a detailed database of sources of dust emissions in Central Asia, from western China to the Caspian Sea, obtained from the analysis of the Moderate Resolution Imaging Spectroradiometer (MODIS) data between 2003 and 2012. A dust enhancement algorithm was employed to obtain two composite images per day at 1 km resolution from MODIS Terra/Aqua acquisitions, from which dust point sources (DPS) were detected by visual analysis and recorded in a database together with meteorological variables at each DPS location. Spatial analysis of DPS has revealed several active source regions, including some which were not widely discussed in literature before (e.g. Northern Afghanistan sources, Betpak-Dala region in western Kazakhstan). Investigation of land surface characteristics and meteorological conditions at each source region revealed mechanisms for the formation of dust sources, including post-fire wind erosion (e.g. Lake Balkhash basin) and rapid desertification (e.g. the Aral Sea). Different seasonal patterns of dust emissions were observed as well as inter-annual trends. The most notable feature was an increase in dust activity in the Aral Kum.

Bioflocculant production and biosorption of zinc and lead by a novel bacterial species, Achromobacter sp. TERI-IASST N, isolated from oil refinery waste.

PubMed

Subudhi, Sanjukta; Batta, Neha; Pathak, Mihirjyoti; Bisht, Varsha; Devi, Arundhuti; Lal, Banwari; Al khulifah, Bader

2014-10-01

A bioflocculant-producing bacterial isolate designated as 'TERI-IASST N' was isolated from activated sludge samples collected from an oil refinery. This isolate demonstrated maximum bioflocculation activity (74%) from glucose among 15 different bioflocculant-producing bacterial strains isolated from the sludge samples and identified as Achromobacter sp. based on 16S rRNA gene sequence. Optimization of pH and supplementation of urea as nitrogen source in the production medium enhanced the flocculation activity of strain TERI-IASST N to 84% (at pH 6). This strain revealed maximum flocculation activity (90%) from sucrose compared to the flocculation activity observed from other carbon sources as investigated (glucose, lactose, fructose, maltose and starch). Ca(2+) served as the suitable divalent cation for maximum bioflocculation activity of TERI-IASST strain N. Maximum flocculation activity was observed at optimum C/N ratio of 1. Flocculation activity of this strain decreased to 75% in the presence of heavy metals; Zn, Pb, Ni, Cu and Cd. In addition strain N revealed considerable biosorption of Zn (430mgL(-1)) and Pb (30mgL(-1)). Bioflocculant yield of strain N was 10.5gL(-1). Fourier transform infrared spectrum indicated the presence of carboxyl, hydroxyl, and amino groups, typical of glycoprotein. Spectroscopic analysis of bioflocculant by nuclear magnetic resonance revealed that it is a glycoprotein, consisting of 57% total sugar and 13% protein. Copyright © 2014 Elsevier Ltd. All rights reserved.

Feminist identity as a predictor of eating disorder diagnostic status.

PubMed

Green, Melinda A; Scott, Norman A; Riopel, Cori M; Skaggs, Anna K

2008-06-01

Passive Acceptance (PA) and Active Commitment (AC) subscales of the Feminist Identity Development Scale (FIDS) were examined as predictors of eating disorder diagnostic status as assessed by the Questionnaire for Eating Disorder Diagnoses (Q-EDD). Results of a hierarchical regression analysis revealed PA and AC scores were not statistically significant predictors of ED diagnostic status after controlling for diagnostic subtype. Results of a multiple regression analysis revealed FIDS as a statistically significant predictor of ED diagnostic status when failing to control for ED diagnostic subtype. Discrepancies suggest ED diagnostic subtype may serve as a moderator variable in the relationship between ED diagnostic status and FIDS. (c) 2008 Wiley Periodicals, Inc.

Analysis of Medium-Chain-Length Polyhydroxyalkanoate-Producing Bacteria in Activated Sludge Samples Enriched by Aerobic Periodic Feeding.

PubMed

Lee, Sun Hee; Kim, Jae Hee; Chung, Chung-Wook; Kim, Do Young; Rhee, Young Ha

2018-04-01

Analysis of mixed microbial populations responsible for the production of medium-chain-length polyhydroxyalkanoates (MCL-PHAs) under periodic substrate feeding in a sequencing batch reactor (SBR) was conducted. Regardless of activated sludge samples and the different MCL alkanoic acids used as the sole external carbon substrate, denaturing gradient gel electrophoresis analysis indicated that Pseudomonas aeruginosa was the dominant bacterium enriched during the SBR process. Several P. aeruginosa strains were isolated from the enriched activated sludge samples. The isolates were subdivided into two groups, one that produced only MCL-PHAs and another that produced both MCL- and short-chain-length PHAs. The SBR periodic feeding experiments with five representative MCL-PHA-producing Pseudomonas species revealed that P. aeruginosa has an advantage over other species that enables it to become dominant in the bacterial community.

Effect of local and global geomagnetic activity on human cardiovascular homeostasis.

PubMed

Dimitrova, Svetla; Stoilova, Irina; Yanev, Toni; Cholakov, Ilia

2004-02-01

The authors investigated the effects of local and planetary geomagnetic activity on human physiology. They collected data in Sofia, Bulgaria, from a group of 86 volunteers during the periods of the autumnal and vernal equinoxes. They used the factors local/planetary geomagnetic activity, day of measurement, gender, and medication use to apply a four-factor multiple analysis of variance. They also used a post hoc analysis to establish the statistical significance of the differences between the average values of the measured physiological parameters in the separate factor levels. In addition, the authors performed correlation analysis between the physiological parameters examined and geophysical factors. The results revealed that geomagnetic changes had a statistically significant influence on arterial blood pressure. Participants expressed this reaction with weak local geomagnetic changes and when major and severe global geomagnetic storms took place.

Implicit timing activates the left inferior parietal cortex.

PubMed

Wiener, Martin; Turkeltaub, Peter E; Coslett, H Branch

2010-11-01

Coull and Nobre (2008) suggested that tasks that employ temporal cues might be divided on the basis of whether these cues are explicitly or implicitly processed. Furthermore, they suggested that implicit timing preferentially engages the left cerebral hemisphere. We tested this hypothesis by conducting a quantitative meta-analysis of eleven neuroimaging studies of implicit timing using the activation-likelihood estimation (ALE) algorithm (Turkeltaub, Eden, Jones, & Zeffiro, 2002). Our analysis revealed a single but robust cluster of activation-likelihood in the left inferior parietal cortex (supramarginal gyrus). This result is in accord with the hypothesis that the left hemisphere subserves implicit timing mechanisms. Furthermore, in conjunction with a previously reported meta-analysis of explicit timing tasks, our data support the claim that implicit and explicit timing are supported by at least partially distinct neural structures. Copyright © 2010 Elsevier Ltd. All rights reserved.

Stimulus-related independent component and voxel-wise analysis of human brain activity during free viewing of a feature film.

PubMed

Lahnakoski, Juha M; Salmi, Juha; Jääskeläinen, Iiro P; Lampinen, Jouko; Glerean, Enrico; Tikka, Pia; Sams, Mikko

2012-01-01

Understanding how the brain processes stimuli in a rich natural environment is a fundamental goal of neuroscience. Here, we showed a feature film to 10 healthy volunteers during functional magnetic resonance imaging (fMRI) of hemodynamic brain activity. We then annotated auditory and visual features of the motion picture to inform analysis of the hemodynamic data. The annotations were fitted to both voxel-wise data and brain network time courses extracted by independent component analysis (ICA). Auditory annotations correlated with two independent components (IC) disclosing two functional networks, one responding to variety of auditory stimulation and another responding preferentially to speech but parts of the network also responding to non-verbal communication. Visual feature annotations correlated with four ICs delineating visual areas according to their sensitivity to different visual stimulus features. In comparison, a separate voxel-wise general linear model based analysis disclosed brain areas preferentially responding to sound energy, speech, music, visual contrast edges, body motion and hand motion which largely overlapped the results revealed by ICA. Differences between the results of IC- and voxel-based analyses demonstrate that thorough analysis of voxel time courses is important for understanding the activity of specific sub-areas of the functional networks, while ICA is a valuable tool for revealing novel information about functional connectivity which need not be explained by the predefined model. Our results encourage the use of naturalistic stimuli and tasks in cognitive neuroimaging to study how the brain processes stimuli in rich natural environments.

Stimulus-Related Independent Component and Voxel-Wise Analysis of Human Brain Activity during Free Viewing of a Feature Film

PubMed Central

Lahnakoski, Juha M.; Salmi, Juha; Jääskeläinen, Iiro P.; Lampinen, Jouko; Glerean, Enrico; Tikka, Pia; Sams, Mikko

2012-01-01

Understanding how the brain processes stimuli in a rich natural environment is a fundamental goal of neuroscience. Here, we showed a feature film to 10 healthy volunteers during functional magnetic resonance imaging (fMRI) of hemodynamic brain activity. We then annotated auditory and visual features of the motion picture to inform analysis of the hemodynamic data. The annotations were fitted to both voxel-wise data and brain network time courses extracted by independent component analysis (ICA). Auditory annotations correlated with two independent components (IC) disclosing two functional networks, one responding to variety of auditory stimulation and another responding preferentially to speech but parts of the network also responding to non-verbal communication. Visual feature annotations correlated with four ICs delineating visual areas according to their sensitivity to different visual stimulus features. In comparison, a separate voxel-wise general linear model based analysis disclosed brain areas preferentially responding to sound energy, speech, music, visual contrast edges, body motion and hand motion which largely overlapped the results revealed by ICA. Differences between the results of IC- and voxel-based analyses demonstrate that thorough analysis of voxel time courses is important for understanding the activity of specific sub-areas of the functional networks, while ICA is a valuable tool for revealing novel information about functional connectivity which need not be explained by the predefined model. Our results encourage the use of naturalistic stimuli and tasks in cognitive neuroimaging to study how the brain processes stimuli in rich natural environments. PMID:22496909

[Factors Influencing Physical Activity among Community-dwelling Older Adults with Type 2 Diabetes: A Path Analysis].

PubMed

Jang, Sun Joo; Park, Hyunju; Kim, Hyunjung; Chang, Sun Ju

2015-06-01

The purpose of the study was to identify factors influencing physical activity among community-dwelling older adults with type 2 diabetes. The study design was based on the Theory of Triadic Influence. A total of 242 older adults with type 2 diabetes participated in this study. Six variables related to physical activity in older adults, including self-efficacy, social normative belief, attitudes, intention, experience, and level of physical activity, were measured using reliable instruments. Data were analyzed using descriptive statistics, Pearson's correlation analyses, and a path analysis. The mean physical activity score was 104.2, range from zero to 381.21. The path analysis showed that self-efficacy had the greatest total effect on physical activity. Also, experience had direct and total effects on physical activity as well as mediated the paths of social normative beliefs to attitudes and intention to physical activity. These factors accounted for 10% of the total variance, and the fit indices of the model satisfied the criteria of fitness. The findings of the study reveal the important role of self-efficacy and past experience in physical activity in older adults with type 2 diabetes.

Neural Networks Involved in Adolescent Reward Processing: An Activation Likelihood Estimation Meta-Analysis of Functional Neuroimaging Studies

PubMed Central

Silverman, Merav H.; Jedd, Kelly; Luciana, Monica

2015-01-01

Behavioral responses to, and the neural processing of, rewards change dramatically during adolescence and may contribute to observed increases in risk-taking during this developmental period. Functional MRI (fMRI) studies suggest differences between adolescents and adults in neural activation during reward processing, but findings are contradictory, and effects have been found in non-predicted directions. The current study uses an activation likelihood estimation (ALE) approach for quantitative meta-analysis of functional neuroimaging studies to: 1) confirm the network of brain regions involved in adolescents’ reward processing, 2) identify regions involved in specific stages (anticipation, outcome) and valence (positive, negative) of reward processing, and 3) identify differences in activation likelihood between adolescent and adult reward-related brain activation. Results reveal a subcortical network of brain regions involved in adolescent reward processing similar to that found in adults with major hubs including the ventral and dorsal striatum, insula, and posterior cingulate cortex (PCC). Contrast analyses find that adolescents exhibit greater likelihood of activation in the insula while processing anticipation relative to outcome and greater likelihood of activation in the putamen and amygdala during outcome relative to anticipation. While processing positive compared to negative valence, adolescents show increased likelihood for activation in the posterior cingulate cortex (PCC) and ventral striatum. Contrasting adolescent reward processing with the existing ALE of adult reward processing (Liu et al., 2011) reveals increased likelihood for activation in limbic, frontolimbic, and striatal regions in adolescents compared with adults. Unlike adolescents, adults also activate executive control regions of the frontal and parietal lobes. These findings support hypothesized elevations in motivated activity during adolescence. PMID:26254587

O6-methylguanine-DNA methyltransferase activity is associated with response to alkylating agent therapy and with MGMT promoter methylation in glioblastoma and anaplastic glioma

PubMed Central

Bobola, Michael S.; Alnoor, Mohammad; Chen, John Y.-S.; Kolstoe, Douglas D.; Silbergeld, Daniel L.; Rostomily, Robert C.; Blank, A.; Chamberlain, Marc C.; Silber, John R.

2014-01-01

Background CpG methylation in the O6-methylguanine-DNA methyltransferase (MGMT) promoter is associated with better outcome following alkylating agent chemotherapy in glioblastoma (GBM) and anaplastic glioma (AG). To what extent improved response reflects low or absent MGMT activity in glioma tissue has not been unequivocally assessed. This information is central to developing anti-resistance therapies. Methods We examined the relationship of MGMT activity in 91 GBMs and 84 AGs with progression-free survival (PFS) following alkylator therapy and with promoter methylation status determined by methylation-specific PCR (MSP). Results Cox regression analysis revealed that GBMs with high activity had a significantly greater risk for progression in dichotomous (P ≤ 0.001) and continuous (P ≤ 0.003) models, an association observed for different alkylator regimens, including concurrent chemo-radiation with temozolomide. Analysis of MGMT promoter methylation status in 47 of the GBMs revealed that methylated tumors had significantly lower activity (P ≤ 0.005) and longer PFS (P ≤ 0.036) compared to unmethylated tumors, despite overlapping activities. PFS was also significantly greater in methylated vs. unmethylated GBMs with comparable activity (P ≤ 0.005), and among unmethylated tumors with less than median activity (P ≤ 0.026), suggesting that mechanisms in addition to MGMT promote alkylator resistance. Similar associations of MGMT activity with PFS and promoter methylation status were observed for AGs. Conclusions Our results provide strong support for the hypotheses that MGMT activity promotes alkylator resistance and reflects promoter methylation status in malignant gliomas. General significance MGMT activity is an attractive target for anti-resistance therapy regardless of methylation status. PMID:25558448

Effects of Different Organic Manures on the Biochemical and Microbial Characteristics of Albic Paddy Soil in a Short-Term Experiment

PubMed Central

Zhang, Qian; Zhou, Wei; Liang, Guoqing; Wang, Xiubin; Sun, Jingwen; He, Ping; Li, Lujiu

2015-01-01

This study aimed to evaluate the effects of chemical fertilizer (NPK), NPK with livestock manure (NPK+M), NPK with straw (NPK+S), and NPK with green manure (NPK+G) on soil enzyme activities and microbial characteristics of albic paddy soil, which is a typical soil with low productivity in China. The responses of extracellular enzyme activities and the microbial community diversity (determined by phospholipid fatty acid analysis [PLFA] and denaturing gradient gel electrophoresis [DGGE]) were measured. The results showed that NPK+M and NPK+S significantly increased rice yield, with NPK+M being approximately 24% greater than NPK. The NPK+M significantly increased soil organic carbon (SOC) and available phosphate (P) and enhanced phosphatase, β-cellobiosidase, L-leucine aminopeptidase and urease activities. The NPK+S significantly increased SOC and available potassium (K) and significantly enhanced N-acetyl-glucosamidase, β-xylosidase, urease, and phenol oxidase activities. The NPK+G significantly improved total nitrogen (N), ammonium N, available P, and N-acetyl-glucosamidase activity. The PLFA biomass was highest under NPK+S, followed by NPK+M and NPK+G treatments. Principal component analysis (PCA) of the PLFA indicated that soils with NPK+M and NPK+S contained higher proportions of unsaturated and cyclopropane fatty acids (biomarkers of fungi and gram-negative bacteria) and soil under NPK+G contained more straight chain saturated fatty acids (representing gram-positive bacteria). PCA of the DGGE patterns showed that organic amendments had a greater influence on fungal community. Cluster analysis of fungal DGGE patterns revealed that NPK+G was clearly separated. Meanwhile, the bacterial community of NPK+M treatment was the most distinct. RDA analysis revealed changes of microbial community composition mostly depended on β-xylosidase, β-cellobiosidase activities, total N and available K contents. The abundances of gram-negative bacterial and fungal PLFAs probably effective in improving fertility of low-yield albic paddy soil because of their significant influence on DGGE profile. PMID:25879759

Effects of different organic manures on the biochemical and microbial characteristics of albic paddy soil in a short-term experiment.

PubMed

Zhang, Qian; Zhou, Wei; Liang, Guoqing; Wang, Xiubin; Sun, Jingwen; He, Ping; Li, Lujiu

2015-01-01

This study aimed to evaluate the effects of chemical fertilizer (NPK), NPK with livestock manure (NPK+M), NPK with straw (NPK+S), and NPK with green manure (NPK+G) on soil enzyme activities and microbial characteristics of albic paddy soil, which is a typical soil with low productivity in China. The responses of extracellular enzyme activities and the microbial community diversity (determined by phospholipid fatty acid analysis [PLFA] and denaturing gradient gel electrophoresis [DGGE]) were measured. The results showed that NPK+M and NPK+S significantly increased rice yield, with NPK+M being approximately 24% greater than NPK. The NPK+M significantly increased soil organic carbon (SOC) and available phosphate (P) and enhanced phosphatase, β-cellobiosidase, L-leucine aminopeptidase and urease activities. The NPK+S significantly increased SOC and available potassium (K) and significantly enhanced N-acetyl-glucosamidase, β-xylosidase, urease, and phenol oxidase activities. The NPK+G significantly improved total nitrogen (N), ammonium N, available P, and N-acetyl-glucosamidase activity. The PLFA biomass was highest under NPK+S, followed by NPK+M and NPK+G treatments. Principal component analysis (PCA) of the PLFA indicated that soils with NPK+M and NPK+S contained higher proportions of unsaturated and cyclopropane fatty acids (biomarkers of fungi and gram-negative bacteria) and soil under NPK+G contained more straight chain saturated fatty acids (representing gram-positive bacteria). PCA of the DGGE patterns showed that organic amendments had a greater influence on fungal community. Cluster analysis of fungal DGGE patterns revealed that NPK+G was clearly separated. Meanwhile, the bacterial community of NPK+M treatment was the most distinct. RDA analysis revealed changes of microbial community composition mostly depended on β-xylosidase, β-cellobiosidase activities, total N and available K contents. The abundances of gram-negative bacterial and fungal PLFAs probably effective in improving fertility of low-yield albic paddy soil because of their significant influence on DGGE profile.

Functional mapping of language networks in the normal brain using a word-association task.

PubMed

Ghosh, Shantanu; Basu, Amrita; Kumaran, Senthil S; Khushu, Subash

2010-08-01

Language functions are known to be affected in diverse neurological conditions, including ischemic stroke, traumatic brain injury, and brain tumors. Because language networks are extensive, interpretation of functional data depends on the task completed during evaluation. The aim was to map the hemodynamic consequences of word association using functional magnetic resonance imaging (fMRI) in normal human subjects. Ten healthy subjects underwent fMRI scanning with a postlexical access semantic association task vs lexical processing task. The fMRI protocol involved a T2*-weighted gradient-echo echo-planar imaging (GE-EPI) sequence (TR 4523 ms, TE 64 ms, flip angle 90°) with alternate baseline and activation blocks. A total of 78 scans were taken (interscan interval = 3 s) with a total imaging time of 587 s. Functional data were processed in Statistical Parametric Mapping software (SPM2) with 8-mm Gaussian kernel by convolving the blood oxygenation level-dependent (BOLD) signal with an hemodynamic response function estimated by general linear method to generate SPM{t} and SPM{F} maps. Single subject analysis of the functional data (FWE-corrected, P≤0.001) revealed extensive activation in the frontal lobes, with overlaps among middle frontal gyrus (MFG), superior, and inferior frontal gyri. BOLD activity was also found in the medial frontal gyrus, middle occipital gyrus (MOG), anterior fusiform gyrus, superior and inferior parietal lobules, and to a smaller extent, the thalamus and right anterior cerebellum. Group analysis (FWE-corrected, P≤0.001) revealed neural recruitment of bilateral lingual gyri, left MFG, bilateral MOG, left superior occipital gyrus, left fusiform gyrus, bilateral thalami, and right cerebellar areas. Group data analysis revealed a cerebellar-occipital-fusiform-thalamic network centered around bilateral lingual gyri for word association, thereby indicating how these areas facilitate language comprehension by activating a semantic association network of words processed postlexical access. This finding is important when assessing the extent of cognitive damage and/or recovery and can be used for presurgical planning after optimization.

Early induction of cytokines/cytokine receptors and Cox2, and activation of NF-κB in 4-nitroquinoline 1-oxide-induced murine oral cancer model

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liu, Yu-Ching; Department of Veterinary Medicine, National Chung Hsing University, Taichung 402, Taiwan; Ho, Heng-Chien

2012-07-15

The purpose of this study was to identify the genes induced early in murine oral carcinogenesis. Murine tongue tumors induced by the carcinogen, 4-nitroquinoline 1-oxide (4-NQO), and paired non-tumor tissues were subjected to microarray analysis. Hierarchical clustering of upregulated genes in the tumor tissues revealed an association of induced genes with inflammation. Cytokines/cytokine receptors induced early were subsequently identified, clearly indicating their involvement in oral carcinogenesis. Hierarchical clustering also showed that cytokine-mediated inflammation was possibly linked with Mapk6. Cox2 exhibited the greatest extent (9–18 fold) of induction in the microarray data, and its early induction was observed in a 2more » h painting experiment by RT-PCR. MetaCore analysis showed that overexpressed Cox2 may interact with p53 and transcriptionally inhibit expression of several downstream genes. A painting experiment in transgenic mice also demonstrated that NF-κB activates early independently of Cox2 induction. MetaCore analysis revealed the most striking metabolic alterations in tumor tissues, especially in lipid metabolism resulting from the reduction of Pparα and Rxrg. Reduced expression of Mapk12 was noted, and MetaCore analysis established its relationship with decreased efficiency of Pparα phosphorylation. In conclusion, in addition to cytokines/cytokine receptors, the early induction of Cox2 and NF-κB activation is involved in murine oral carcinogenesis.« less

Developmental specialization in the right intraparietal sulcus for the abstract representation of numerical magnitude.

PubMed

Holloway, Ian D; Ansari, Daniel

2010-11-01

Because number is an abstract quality of a set, the way in which a number is externally represented does not change its quantitative meaning. In this study, we examined the development of the brain regions that support format-independent representation of numerical magnitude. We asked children and adults to perform both symbolic (Hindu-Arabic numerals) and nonsymbolic (arrays of squares) numerical comparison tasks as well as two control tasks while their brains were scanned using fMRI. In a preliminary analysis, we calculated the conjunction between symbolic and nonsymbolic numerical comparison. We then examined in which brain regions this conjunction differed between children and adults. This analysis revealed a large network of visual and parietal regions that showed greater activation in adults relative to children. In our primary analysis, we examined age-related differences in the conjunction of symbolic and nonsymbolic comparison after subtracting the control tasks. This analysis revealed a much more limited set of regions including the right inferior parietal lobe near the intraparietal sulcus. In addition to showing increased activation to both symbolic and nonsymbolic magnitudes over and above activation related to response selection, this region showed age-related differences in the distance effect. Our findings demonstrate that the format-independent representation of numerical magnitude in the right inferior parietal lobe is the product of developmental processes of cortical specialization and highlight the importance of using appropriate control tasks when conducting developmental neuroimaging studies.

Visual target modulation of functional connectivity networks revealed by self-organizing group ICA.

PubMed

van de Ven, Vincent; Bledowski, Christoph; Prvulovic, David; Goebel, Rainer; Formisano, Elia; Di Salle, Francesco; Linden, David E J; Esposito, Fabrizio

2008-12-01

We applied a data-driven analysis based on self-organizing group independent component analysis (sogICA) to fMRI data from a three-stimulus visual oddball task. SogICA is particularly suited to the investigation of the underlying functional connectivity and does not rely on a predefined model of the experiment, which overcomes some of the limitations of hypothesis-driven analysis. Unlike most previous applications of ICA in functional imaging, our approach allows the analysis of the data at the group level, which is of particular interest in high order cognitive studies. SogICA is based on the hierarchical clustering of spatially similar independent components, derived from single subject decompositions. We identified four main clusters of components, centered on the posterior cingulate, bilateral insula, bilateral prefrontal cortex, and right posterior parietal and prefrontal cortex, consistently across all participants. Post hoc comparison of time courses revealed that insula, prefrontal cortex and right fronto-parietal components showed higher activity for targets than for distractors. Activation for distractors was higher in the posterior cingulate cortex, where deactivation was observed for targets. While our results conform to previous neuroimaging studies, they also complement conventional results by showing functional connectivity networks with unique contributions to the task that were consistent across subjects. SogICA can thus be used to probe functional networks of active cognitive tasks at the group-level and can provide additional insights to generate new hypotheses for further study. Copyright 2007 Wiley-Liss, Inc.

A cytocidal tissue kallikrein isolated from mouse submandibular glands.

PubMed

Murakami, K; Ikigai, H; Nagumo, N; Tomita, M; Shimamura, T

1989-11-06

A cytocidal factor against mouse thymocytes was purified from the submandibular glands of female BALB/c mice using Sephadex G-50 gel filtration chromatography and reverse-phase HPLC. SDS-PAGE and amino acid sequence analysis revealed that the cytocidal factor was mouse glandular kallikrein (mGK)-6. mGK-6 showed an optimal enzyme activity at pH 10 and a cytocidal activity against thymocytes in a dose-dependent manner.

Down-regulation of HSP60 Suppresses the Proliferation of Glioblastoma Cells via the ROS/AMPK/mTOR Pathway

PubMed Central

Tang, Haiping; Li, Jin; Liu, Xiaohui; Wang, Guihuai; Luo, Minkui; Deng, Haiteng

2016-01-01

Glioblastoma is a fatal and incurable cancer with the hyper-activated mTOR pathway. HSP60, a major chaperone for maintenance of mitochondrial proteostasis, is highly expressed in glioblastoma patients. To understand the effects of HSP60 on glioblastoma tumorigenesis and progression, we characterized the HSP60-knockdowned glioblastoma cells and revealed that HSP60 silencing markedly suppressed cell proliferation and promoted cell to undergo the epithelial-mesenchymal transition (EMT). Proteomic analysis showed that ribosomal proteins were significantly downregulated whereas EMT-associated proteins were up-regulated in HSP60-knockdowned U87 cells as confirmed by a distinct enrichment pattern in newly synthesized proteins with azido-homoalanine labeling. Biochemical analysis revealed that HSP60 knockdown increased reactive oxygen species (ROS) production that led to AMPK activation, similarly to the complex I inhibitor rotenone-induced AMPK activation. Activated AMPK suppressed mTORC1 mediated S6K and 4EBP1 phosphorylation to decrease protein translation, which slowed down cell growth and proliferation. On the other hand, high levels of ROS in HSP60 knockdowned or rotenone-treated U87 cells contributed to EMT. These results indicate that HSP60 silencing deactivates the mTOR pathway to suppress glioblastoma progression, suggesting that HSP60 is a potential therapeutic target for glioblastoma treatment. PMID:27325206

Oxidative stress and spermatogenesis suppression in the testis of cadmium-treated Bombyx mori larvae.

PubMed

Yuan, Hongxia; Qin, Fenjv; Guo, Weiqiang; Gu, Huajie; Shao, Aihua

2016-03-01

Bombyx mori L. (B. mori) were exposed to cadmium chloride (CdCl2) incorporated in an artificial diet (0, 6.25, 12.5, 25, and 50 mg kg(-1)) throughout the larval stage. Changes in malondialdehyde (MDA) and reduced glutathione (GSH) contents and activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px), as well as their corresponding messenger RNA (mRNA) levels in the testes of the fifth instar larvae were evaluated. Additionally, spermatozoon deformation in the testes was examined. Upon Cd treatment, the MDA content in the testes was significantly increased in a concentration-dependent manner. Cd-exposed larvae had increased levels of glutathione. Pearson's correlation analysis revealed that SOD and CAT activities were positively correlated (R (2) = 0.605, P = 0.017). The changing trends in the mRNA levels of these enzymes were not always consistent with those of enzymatic activities. Alterations in GSH-Px activities and mRNA levels were positively correlated (R (2) = 0.771, P < 0.01). Morphological analysis revealed that Cd deformed and affected the maturation of spermatozoa. Our results collectively support a relationship between Cd and alterations in the levels of antioxidant enzymes in B. mori testes.

Evaluation of Toxicity and Antimicrobial Activity of an Ethanolic Extract from Leaves of Morus alba L. (Moraceae)

PubMed Central

de Oliveira, Alisson Macário; Mesquita, Matheus da Silva; da Silva, Gabriela Cavalcante; de Oliveira Lima, Edeltrudes; de Medeiros, Paloma Lys; Paiva, Patrícia Maria Guedes; de Souza, Ivone Antônia; Napoleão, Thiago Henrique

2015-01-01

This work evaluated an ethanolic extract from Morus alba leaves for toxicity to Artemia salina, oral toxicity to mice, and antimicrobial activity. Phytochemical analysis revealed the presence of coumarins, flavonoids, tannins, and triterpenes in the extract, which did not show toxicity to A. salina nauplii. No mortality and behavioral alterations were detected for mice treated with the extract (300 and 2000 mg/kg b.w.) for 14 days. However, animals that received the highest dose showed reduced MCV and MCHC as well as increased serum alkaline phosphatase activity. In treatments with the extract at both 300 and 2000 mg/kg, there was a reduction in number of leukocytes, with decrease in percentage of lymphocytes and increase in proportion of segmented cells. Histopathological analysis of organs from mice treated with the extract at 2000 mg/kg revealed turgidity of contorted tubules in kidneys, presence of leukocyte infiltration around the liver centrilobular vein, and high dispersion of the spleen white pulp. The extract showed antimicrobial activity against Staphylococcus aureus, Pseudomonas aeruginosa, Candida albicans, Candida krusei, Candida tropicalis, and Aspergillus flavus. In conclusion, the extract contains antimicrobial agents and was not lethal for mice when ingested; however, its use requires caution because it promoted biochemical, hematological, and histopathological alterations. PMID:26246840

5-Hydroxyferulic acid methyl ester isolated from wasabi leaves inhibits 3T3-L1 adipocyte differentiation.

PubMed

Misawa, Naoki; Hosoya, Takahiro; Yoshida, Shuhei; Sugimoto, Osamu; Yamada-Kato, Tomoe; Kumazawa, Shigenori

2018-02-26

To investigate the compounds present in wasabi leaves (Wasabia japonica Matsumura) that inhibit the adipocyte differentiation, activity-guided fractionation was performed on these leaves. 5-Hydroxyferulic acid methyl ester (1: 5-HFA ester), one of the phenylpropanoids, was isolated from wasabi leaves as a compound that inhibits the adipocyte differentiation. Compound 1 suppressed the intracellular lipid accumulation of 3T3-L1 cells without significant cytotoxicity. Gene expression analysis revealed that 1 suppressed the mRNA expression of 2 master regulators of adipocyte differentiation, PPARγ and C/EBPα. Furthermore, 1 downregulated the expression of adipogenesis-related genes, GLUT4, LPL, SREBP-1c, ACC, and FAS. Protein expression analysis revealed that 1 suppressed PPARγ protein expression. Moreover, to investigate the relationship between the structure and activity of inhibiting the adipocyte differentiation, we synthesized 12 kinds of phenylpropanoid analog. Comparison of the activity among 1 and its analogs suggested that the compound containing the substructure that possess a common functional group at the ortho position such as a catechol group exhibits the activity of inhibiting the adipocyte differentiation. Taken together, our findings suggest that 1 from wasabi leaves inhibits adipocyte differentiation via the downregulation of PPARγ. Copyright © 2018 John Wiley & Sons, Ltd.

Using factor analysis to identify neuromuscular synergies during treadmill walking

NASA Technical Reports Server (NTRS)

Merkle, L. A.; Layne, C. S.; Bloomberg, J. J.; Zhang, J. J.

1998-01-01

Neuroscientists are often interested in grouping variables to facilitate understanding of a particular phenomenon. Factor analysis is a powerful statistical technique that groups variables into conceptually meaningful clusters, but remains underutilized by neuroscience researchers presumably due to its complicated concepts and procedures. This paper illustrates an application of factor analysis to identify coordinated patterns of whole-body muscle activation during treadmill walking. Ten male subjects walked on a treadmill (6.4 km/h) for 20 s during which surface electromyographic (EMG) activity was obtained from the left side sternocleidomastoid, neck extensors, erector spinae, and right side biceps femoris, rectus femoris, tibialis anterior, and medial gastrocnemius. Factor analysis revealed 65% of the variance of seven muscles sampled aligned with two orthogonal factors, labeled 'transition control' and 'loading'. These two factors describe coordinated patterns of muscular activity across body segments that would not be evident by evaluating individual muscle patterns. The results show that factor analysis can be effectively used to explore relationships among muscle patterns across all body segments to increase understanding of the complex coordination necessary for smooth and efficient locomotion. We encourage neuroscientists to consider using factor analysis to identify coordinated patterns of neuromuscular activation that would be obscured using more traditional EMG analyses.

Quercetin-Iron Complex: Synthesis, Characterization, Antioxidant, DNA Binding, DNA Cleavage, and Antibacterial Activity Studies.

PubMed

Raza, Aun; Xu, Xiuquan; Xia, Li; Xia, Changkun; Tang, Jian; Ouyang, Zhen

2016-11-01

Quercetin-iron (II) complex was synthesized and characterized by elemental analysis, ultraviolet-visible spectrophotometry, fourier transform infrared spectroscopy, mass spectrometry, proton nuclear magnetic resonance spectroscopy, thermogravimetry and differential scanning calorimetry, scanning electron micrography and molar conductivity. The low molar conductivity value investigates the non-electrolyte nature of the complex. The elemental analysis and other physical and spectroscopic methods reveal the 1:2 stoichiometric ratio (metal:ligand) of the complex. Antioxidant study of the quercetin and its metal complex against 2, 2-di-phenyl-1-picryl hydrazyl radical showed that the complex has much more radical scavenging activity than free quercetin. The interaction of quercetin-iron (II) complex with DNA was determined using ultraviolet visible spectra, fluorescence spectra and agarose gel electrophoresis. The results showed that quercetin-iron (II) complex can intercalate moderately with DNA, quench a strong intercalator ethidium bromide and compete for the intercalative binding sites. The complex showed significant cleavage of pBR 322 DNA from supercoiled form to nicked circular form and these cleavage effects were dose-dependent. Moreover, the mechanism of DNA cleavage indicated that it was an oxidative cleavage pathway. These results revealed the potential nuclease activity of complex to cleave DNA. In addition, antibacterial activity of complex on E.coli and S. aureus was also investigated. The results showed that complex has higher antibacterial activity than ligand.

Inhibition of MAO-A and stimulation of behavioural activities in mice by the inactive prodrug form of the anti-influenza agent oseltamivir.

PubMed

Hiasa, Miki; Isoda, Yumiko; Kishimoto, Yasushi; Saitoh, Kenta; Kimura, Yasuaki; Kanai, Motomu; Shibasaki, Masakatsu; Hatakeyama, Dai; Kirino, Yutaka; Kuzuhara, Takashi

2013-05-01

Oseltamivir is the most widely prescribed anti-influenza medication. However, in rare instances, it has been reported to stimulate behavioural activities in adolescents. The goal of this study was to determine the molecular mechanism responsible for these behavioural activities. We performed an in vitro assay of MAO-A, the enzyme responsible for neurotransmitter degradation, using either the active form - oseltamivir carboxylate (OC) or the inactive prodrug - oseltamivir ethyl ester (OEE). We also analysed the docking of MAO-A with OEE or OC in silico. Mouse behaviours after OEE or OC administration were monitored using automated video and computer analysis. OEE, but not OC, competitively and selectively inhibited human MAO-A. The estimated Ki value was comparable with the Km values of native substrates of MAO-A. Docking simulations in silico based on the tertiary structure of MAO-A suggested that OEE could fit into the inner pocket of the enzyme. Behavioural monitoring using automated video analysis further revealed that OEE, not OC, significantly enhanced spontaneous behavioural activities in mice, such as jumping, rearing, sniffing, turning and walking. Our multilevel analyses suggested OEE to be the cause of the side effects associated with oseltamivir and revealed the molecular mechanism underlying the stimulated behaviours induced by oseltamivir in some circumstances. © 2013 The Authors. British Journal of Pharmacology © 2013 The British Pharmacological Society.

Inhibition of MAO-A and stimulation of behavioural activities in mice by the inactive prodrug form of the anti-influenza agent oseltamivir

PubMed Central

Hiasa, Miki; Isoda, Yumiko; Kishimoto, Yasushi; Saitoh, Kenta; Kimura, Yasuaki; Kanai, Motomu; Shibasaki, Masakatsu; Hatakeyama, Dai; Kirino, Yutaka; Kuzuhara, Takashi

2013-01-01

Background and Purpose Oseltamivir is the most widely prescribed anti-influenza medication. However, in rare instances, it has been reported to stimulate behavioural activities in adolescents. The goal of this study was to determine the molecular mechanism responsible for these behavioural activities. Experimental Approach We performed an in vitro assay of MAO-A, the enzyme responsible for neurotransmitter degradation, using either the active form – oseltamivir carboxylate (OC) or the inactive prodrug – oseltamivir ethyl ester (OEE). We also analysed the docking of MAO-A with OEE or OC in silico. Mouse behaviours after OEE or OC administration were monitored using automated video and computer analysis. Key Results OEE, but not OC, competitively and selectively inhibited human MAO-A. The estimated Ki value was comparable with the Km values of native substrates of MAO-A. Docking simulations in silico based on the tertiary structure of MAO-A suggested that OEE could fit into the inner pocket of the enzyme. Behavioural monitoring using automated video analysis further revealed that OEE, not OC, significantly enhanced spontaneous behavioural activities in mice, such as jumping, rearing, sniffing, turning and walking. Conclusions and Implications Our multilevel analyses suggested OEE to be the cause of the side effects associated with oseltamivir and revealed the molecular mechanism underlying the stimulated behaviours induced by oseltamivir in some circumstances. PMID:23320399

Automated video analysis system reveals distinct diurnal behaviors in C57BL/6 and C3H/HeN mice.

PubMed

Adamah-Biassi, E B; Stepien, I; Hudson, R L; Dubocovich, M L

2013-04-15

Advances in rodent behavior dissection using automated video recording and analysis allows detailed phenotyping. This study compared and contrasted 15 diurnal behaviors recorded continuously using an automated behavioral analysis system for a period of 14 days under a 14/10 light/dark cycle in single housed C3H/HeN (C3H) or C57BL/6 (C57) male mice. Diurnal behaviors, recorded with minimal experimental interference and analyzed using phenotypic array and temporal distribution analysis showed bimodal and unimodal profiles in the C57 and C3H mice, respectively. Phenotypic array analysis revealed distinct behavioral rhythms in Activity-Like Behaviors (i.e. walk, hang, jump, come down) (ALB), Exploration-Like Behaviors (i.e. dig, groom, rear up, sniff, stretch) (ELB), Ingestion-Like Behaviors (i.e. drink, eat) (ILB) and Resting-Like Behaviors (i.e. awake, remain low, rest, twitch) (RLB) of C3H and C57 mice. Temporal distribution analysis demonstrated that strain and time of day affects the magnitude and distribution of the spontaneous homecage behaviors. Wheel running activity, water and food measurements correlated with timing of homecage behaviors. Subcutaneous (3 mg/kg, sc) or oral (0.02 mg/ml, oral) melatonin treatments in C57 mice did not modify either the total 24 h magnitude or temporal distribution of homecage behaviors when compared with vehicle treatments. We conclude that C3H and C57 mice show different spontaneous activity and behavioral rhythms specifically during the night period which are not modulated by melatonin. Copyright © 2013 Elsevier B.V. All rights reserved.

Reflection during Portfolio-Based Conversations

ERIC Educational Resources Information Center

Oosterbaan, Anne E.; van der Schaaf, Marieke F.; Baartman, Liesbeth K. J.; Stokking, Karel M.

2010-01-01

This study aims to explore the relationship between the occurrence of reflection (and non-reflection) and thinking activities (e.g., orientating, selecting, analysing) during portfolio-based conversations. Analysis of 21 transcripts of portfolio-based conversations revealed that 20% of the segments were made up of reflection (content reflection…

Correlation of neural activity with behavioral kinematics reveals distinct sensory encoding and evidence accumulation processes during active tactile sensing.

PubMed

Delis, Ioannis; Dmochowski, Jacek P; Sajda, Paul; Wang, Qi

2018-07-15

Many real-world decisions rely on active sensing, a dynamic process for directing our sensors (e.g. eyes or fingers) across a stimulus to maximize information gain. Though ecologically pervasive, limited work has focused on identifying neural correlates of the active sensing process. In tactile perception, we often make decisions about an object/surface by actively exploring its shape/texture. Here we investigate the neural correlates of active tactile decision-making by simultaneously measuring electroencephalography (EEG) and finger kinematics while subjects interrogated a haptic surface to make perceptual judgments. Since sensorimotor behavior underlies decision formation in active sensing tasks, we hypothesized that the neural correlates of decision-related processes would be detectable by relating active sensing to neural activity. Novel brain-behavior correlation analysis revealed that three distinct EEG components, localizing to right-lateralized occipital cortex (LOC), middle frontal gyrus (MFG), and supplementary motor area (SMA), respectively, were coupled with active sensing as their activity significantly correlated with finger kinematics. To probe the functional role of these components, we fit their single-trial-couplings to decision-making performance using a hierarchical-drift-diffusion-model (HDDM), revealing that the LOC modulated the encoding of the tactile stimulus whereas the MFG predicted the rate of information integration towards a choice. Interestingly, the MFG disappeared from components uncovered from control subjects performing active sensing but not required to make perceptual decisions. By uncovering the neural correlates of distinct stimulus encoding and evidence accumulation processes, this study delineated, for the first time, the functional role of cortical areas in active tactile decision-making. Copyright © 2018 Elsevier Inc. All rights reserved.

Single Molecule Analysis of Serotonin Transporter Regulation Using Antagonist-Conjugated Quantum Dots Reveals Restricted, p38 MAPK-Dependent Mobilization Underlying Uptake Activation

PubMed Central

Chang, Jerry C.; Tomlinson, Ian D.; Warnement, Michael R.; Ustione, Alessandro; Carneiro, Ana M. D.; Piston, David W.; Blakely, Randy D.; Rosenthal, Sandra J.

2012-01-01

The presynaptic serotonin (5-HT) transporter (SERT) is targeted by widely prescribed antidepressant medications. Altered SERT expression or regulation has been implicated in multiple neuropsychiatric disorders, including anxiety, depression and autism. Here, we implement a generalizable strategy that exploits antagonist-conjugated quantum dots (Qdots) to monitor, for the first time, single SERT proteins on the surface of serotonergic cells. We document two pools of SERT proteins defined by lateral mobility, one that exhibits relatively free diffusion, and a second, localized to cholesterol and GM1 ganglioside-enriched microdomains, that displays restricted mobility. Receptor-linked signalling pathways that enhance SERT activity mobilize transporters that, nonetheless, remain confined to membrane microdomains. Mobilization of transporters arise from a p38 MAPK-dependent untethering of the SERT C-terminus from the juxtamembrane actin cytoskeleton. Our studies establish the utility of ligand-conjugated Qdots for analysis of the behaviour of single membrane proteins and reveal a physical basis for signaling-mediated SERT regulation. PMID:22745492

A trypsin inhibitor from Sapindus saponaria L. seeds: purification, characterization, and activity towards pest insect digestive enzyme.

PubMed

Macedo, Maria Lígia R; Diz Filho, Eduardo B S; Freire, Mariadas Graças M; Oliva, Maria Luiza V; Sumikawa, Joana T; Toyama, Marcos H; Marangoni, Sérgio

2011-01-01

The present paper describes the purification, characterization and determination of the partial primary structure of the first trypsin inhibitor isolated from the family Sapindaceae. A highly stable, potent trypsin inhibitor (SSTI) was purified to homogeneity. SDS-PAGE analysis revealed that the protein consists of a two-polypeptide chain with molecular masses of approximately 15 and 3 kDa. The purified inhibitor inhibited bovine trypsin at a 1:1 M ratio. Kinetic analysis revealed that the protein is a competitive inhibitor with an equilibrium dissociation constant of 10⁻⁹ M for trypsin. The partial NH₂- terminal sequence of 36 amino acids in SSTI indicates homology with other members of the trypsin-inhibitor family from different sources. This inhibitor is highly stable in the presence of denaturing agents. SSTI showed significant inhibitory activity against trypsin-like proteases present in the larval midgut on Anagasta kuehniella, Corcyra cephalonica, Diatreae saccharalis and Anticarsia gemmatalis.

Structure of the Siz/PIAS SUMO E3 ligase Siz1 and determinants required for SUMO modification of PCNA

PubMed Central

Yunus, Ali A.; Lima, Christopher D.

2009-01-01

Summary Siz1 is a founding member of the Siz/PIAS RING family of SUMO E3 ligases. The x-ray structure of an active Siz1 ligase revealed an elongated tripartite architecture comprised of an N-terminal PINIT domain, a central zinc-containing RING-like SP-RING domain, and a C-terminal domain we term the SP-CTD. Structure-based mutational analysis and biochemical studies show that the SP-RING and SP-CTD are required for activation of the E2~SUMO thioester while the PINIT domain is essential for redirecting SUMO conjugation to the proliferating cell nuclear antigen (PCNA) at lysine 164, a non-consensus lysine residue that is not modified by the SUMO E2 in the absence of Siz1. Mutational analysis of Siz1 and PCNA revealed surfaces on both proteins that are required for efficient SUMO modification of PCNA in vitro and in vivo. PMID:19748360

Label-free quantitative proteomics reveals differentially regulated proteins in the latex of sticky diseased Carica papaya L. plants

PubMed Central

Rodrigues, Silas P.; Ventura, José A.; Aguilar, Clemente; Nakayasu, Ernesto S.; Choi, HyungWon; Sobreira, Tiago J. P.; Nohara, Lilian L.; Wermelinger, Luciana S.; Almeida, Igor C.; Zingali, Russolina B.; Fernandes, Patricia M. B.

2012-01-01

Papaya meleira virus (PMeV) is so far the only described laticifer-infecting virus, the causal agent of papaya (Carica papaya L.) sticky disease. The effects of PMeV on the laticifers’ regulatory network were addressed here through the proteomic analysis of papaya latex. Using both 1-DE- and 1D-LC-ESI-MS/MS, 160 unique papaya latex proteins were identified, representing 122 new proteins in the latex of this plant. Quantitative analysis by normalized spectral counting revealed 10 down-regulated proteins in the latex of diseased plants, 9 cysteine proteases (chymopapain) and 1 latex serine proteinase inhibitor. A repression of papaya latex proteolytic activity during PMeV infection was hypothesized. This was further confirmed by enzymatic assays that showed a reduction of cysteine-protease-associated proteolytic activity in the diseased papaya latex. These findings are discussed in the context of plant responses against pathogens and may greatly contribute to understand the roles of laticifers in plant stress responses. PMID:22465191

Suppression of the µ Rhythm during Speech and Non-Speech Discrimination Revealed by Independent Component Analysis: Implications for Sensorimotor Integration in Speech Processing

PubMed Central

Bowers, Andrew; Saltuklaroglu, Tim; Harkrider, Ashley; Cuellar, Megan

2013-01-01

Background Constructivist theories propose that articulatory hypotheses about incoming phonetic targets may function to enhance perception by limiting the possibilities for sensory analysis. To provide evidence for this proposal, it is necessary to map ongoing, high-temporal resolution changes in sensorimotor activity (i.e., the sensorimotor μ rhythm) to accurate speech and non-speech discrimination performance (i.e., correct trials.) Methods Sixteen participants (15 female and 1 male) were asked to passively listen to or actively identify speech and tone-sweeps in a two-force choice discrimination task while the electroencephalograph (EEG) was recorded from 32 channels. The stimuli were presented at signal-to-noise ratios (SNRs) in which discrimination accuracy was high (i.e., 80–100%) and low SNRs producing discrimination performance at chance. EEG data were decomposed using independent component analysis and clustered across participants using principle component methods in EEGLAB. Results ICA revealed left and right sensorimotor µ components for 14/16 and 13/16 participants respectively that were identified on the basis of scalp topography, spectral peaks, and localization to the precentral and postcentral gyri. Time-frequency analysis of left and right lateralized µ component clusters revealed significant (pFDR<.05) suppression in the traditional beta frequency range (13–30 Hz) prior to, during, and following syllable discrimination trials. No significant differences from baseline were found for passive tasks. Tone conditions produced right µ beta suppression following stimulus onset only. For the left µ, significant differences in the magnitude of beta suppression were found for correct speech discrimination trials relative to chance trials following stimulus offset. Conclusions Findings are consistent with constructivist, internal model theories proposing that early forward motor models generate predictions about likely phonemic units that are then synthesized with incoming sensory cues during active as opposed to passive processing. Future directions and possible translational value for clinical populations in which sensorimotor integration may play a functional role are discussed. PMID:23991030

Suppression of the µ rhythm during speech and non-speech discrimination revealed by independent component analysis: implications for sensorimotor integration in speech processing.

PubMed

Bowers, Andrew; Saltuklaroglu, Tim; Harkrider, Ashley; Cuellar, Megan

2013-01-01

Constructivist theories propose that articulatory hypotheses about incoming phonetic targets may function to enhance perception by limiting the possibilities for sensory analysis. To provide evidence for this proposal, it is necessary to map ongoing, high-temporal resolution changes in sensorimotor activity (i.e., the sensorimotor μ rhythm) to accurate speech and non-speech discrimination performance (i.e., correct trials.). Sixteen participants (15 female and 1 male) were asked to passively listen to or actively identify speech and tone-sweeps in a two-force choice discrimination task while the electroencephalograph (EEG) was recorded from 32 channels. The stimuli were presented at signal-to-noise ratios (SNRs) in which discrimination accuracy was high (i.e., 80-100%) and low SNRs producing discrimination performance at chance. EEG data were decomposed using independent component analysis and clustered across participants using principle component methods in EEGLAB. ICA revealed left and right sensorimotor µ components for 14/16 and 13/16 participants respectively that were identified on the basis of scalp topography, spectral peaks, and localization to the precentral and postcentral gyri. Time-frequency analysis of left and right lateralized µ component clusters revealed significant (pFDR<.05) suppression in the traditional beta frequency range (13-30 Hz) prior to, during, and following syllable discrimination trials. No significant differences from baseline were found for passive tasks. Tone conditions produced right µ beta suppression following stimulus onset only. For the left µ, significant differences in the magnitude of beta suppression were found for correct speech discrimination trials relative to chance trials following stimulus offset. Findings are consistent with constructivist, internal model theories proposing that early forward motor models generate predictions about likely phonemic units that are then synthesized with incoming sensory cues during active as opposed to passive processing. Future directions and possible translational value for clinical populations in which sensorimotor integration may play a functional role are discussed.

Expression analysis revealing destabilizing mutations in phosphomannomutase 2 deficiency (PMM2-CDG): expression analysis of PMM2-CDG mutations.

PubMed

Vega, Ana Isabel; Pérez-Cerdá, Celia; Abia, David; Gámez, Alejandra; Briones, Paz; Artuch, Rafael; Desviat, Lourdes R; Ugarte, Magdalena; Pérez, Belén

2011-08-01

Deficiency of phosphomannomutase (PMM2, MIM#601785) is the most common congenital disorder of glycosylation. Herein we report the genetic analysis of 22 Spanish PMM2 deficient patients and the functional analysis of 14 nucleotide changes in a prokaryotic expression system in order to elucidate their molecular pathogenesis. PMM2 activity assay revealed the presence of six protein changes with no enzymatic activities (p.R123Q, p.R141H, p.F157S, p.P184T, p.F207S and p.D209G) and seven mild protein changes with residual activities ranging from 16 to 54% (p.L32R, p.V44A p.D65Y, p.P113L p.T118S, p.T237M and p.C241S) and also one variant change with normal activity (p.E197A). The results obtained from Western blot analysis, degradation time courses of 11 protein changes and structural analysis of the PMM2 protein, suggest that the loss-of-function of most mutant proteins is based on their increased susceptibility to degradation or aggregation compared to the wild type protein, considering PMM2 deficiency as a conformational disease. We have identified exclusively catalytic protein change (p.D209G), catalytic protein changes affecting protein stability (p.R123Q and p.R141H), two protein changes disrupting the dimer interface (p.P113L and p.T118S) and several misfolding changes (p.L32R, p.V44A, p.D65Y, p.F157S, p.P184T, p.F207S, p.T237M and p.C241S). Our current work opens a promising therapeutic option using pharmacological chaperones to revert the effect of the characterized misfolding mutations identified in a wide range of PMM2 deficient patients.

Anticarcinogenic compounds in the Uzbek medicinal plant, Helichrysum maracandicum.

PubMed

Yagura, Toru; Motomiya, Tomoko; Ito, Michiho; Honda, Gisho; Iida, Akira; Kiuchi, Fumiyuki; Tokuda, Harukuni; Nishino, Hoyoku

2008-04-01

An ethanol extract of Helichrysum maracandicum showed antiproliferative activity against cultured cells of SENCAR mouse in an in vitro assay, and activity-guided fractionation of the extract resulted in the isolation of isosalipurposide as an active substance. Naringenin chalcone, the aglycone of isosalipurposide, also showed strong antiproliferative activity. An in vivo assay of two-stage carcinogenesis on mouse skin revealed that epidermal application of isosalipurposide resulted in delayed formation of papillomas. Western blot analysis showed that the expression of p38 mitogen-activated protein kinase was suppressed by the administration of naringenin chalcone or isosalipurposide, which might be related to the anticarcinogenic activity.

Quantitative Structure-Activity Relationship Modeling Coupled with Molecular Docking Analysis in Screening of Angiotensin I-Converting Enzyme Inhibitory Peptides from Qula Casein Hydrolysates Obtained by Two-Enzyme Combination Hydrolysis.

PubMed

Lin, Kai; Zhang, Lanwei; Han, Xue; Meng, Zhaoxu; Zhang, Jianming; Wu, Yifan; Cheng, Dayou

2018-03-28

In this study, Qula casein derived from yak milk casein was hydrolyzed using a two-enzyme combination approach, and high angiotensin I-converting enzyme (ACE) inhibitory activity peptides were screened by quantitative structure-activity relationship (QSAR) modeling integrated with molecular docking analysis. Hydrolysates (<3 kDa) derived from combinations of thermolysin + alcalase and thermolysin + proteinase K demonstrated high ACE inhibitory activities. Peptide sequences in hydrolysates derived from these two combinations were identified by liquid chromatography-tandem mass spectrometry (LC-MS/MS). On the basis of the QSAR modeling prediction, a total of 16 peptides were selected for molecular docking analysis. The docking study revealed that four of the peptides (KFPQY, MPFPKYP, MFPPQ, and QWQVL) bound the active site of ACE. These four novel peptides were chemically synthesized, and their IC 50 was determined. Among these peptides, KFPQY showed the highest ACE inhibitory activity (IC 50 = 12.37 ± 0.43 μM). Our study indicated that Qula casein presents an excellent source to produce ACE inhibitory peptides.

Impaired social brain network for processing dynamic facial expressions in autism spectrum disorders.

PubMed

Sato, Wataru; Toichi, Motomi; Uono, Shota; Kochiyama, Takanori

2012-08-13

Impairment of social interaction via facial expressions represents a core clinical feature of autism spectrum disorders (ASD). However, the neural correlates of this dysfunction remain unidentified. Because this dysfunction is manifested in real-life situations, we hypothesized that the observation of dynamic, compared with static, facial expressions would reveal abnormal brain functioning in individuals with ASD.We presented dynamic and static facial expressions of fear and happiness to individuals with high-functioning ASD and to age- and sex-matched typically developing controls and recorded their brain activities using functional magnetic resonance imaging (fMRI). Regional analysis revealed reduced activation of several brain regions in the ASD group compared with controls in response to dynamic versus static facial expressions, including the middle temporal gyrus (MTG), fusiform gyrus, amygdala, medial prefrontal cortex, and inferior frontal gyrus (IFG). Dynamic causal modeling analyses revealed that bi-directional effective connectivity involving the primary visual cortex-MTG-IFG circuit was enhanced in response to dynamic as compared with static facial expressions in the control group. Group comparisons revealed that all these modulatory effects were weaker in the ASD group than in the control group. These results suggest that weak activity and connectivity of the social brain network underlie the impairment in social interaction involving dynamic facial expressions in individuals with ASD.

Analysis of in vitro evolution reveals the underlying distribution of catalytic activity among random sequences.

PubMed

Pressman, Abe; Moretti, Janina E; Campbell, Gregory W; Müller, Ulrich F; Chen, Irene A

2017-08-21

The emergence of catalytic RNA is believed to have been a key event during the origin of life. Understanding how catalytic activity is distributed across random sequences is fundamental to estimating the probability that catalytic sequences would emerge. Here, we analyze the in vitro evolution of triphosphorylating ribozymes and translate their fitnesses into absolute estimates of catalytic activity for hundreds of ribozyme families. The analysis efficiently identified highly active ribozymes and estimated catalytic activity with good accuracy. The evolutionary dynamics follow Fisher's Fundamental Theorem of Natural Selection and a corollary, permitting retrospective inference of the distribution of fitness and activity in the random sequence pool for the first time. The frequency distribution of rate constants appears to be log-normal, with a surprisingly steep dropoff at higher activity, consistent with a mechanism for the emergence of activity as the product of many independent contributions. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

Magnetic resonance enteroclysis in patients with Crohn's disease: fat saturated T2-weighted sequences for evaluation of inflammatory activity.

PubMed

Grieser, Christian; Denecke, Timm; Steffen, Ingo G; Werner, Scarlett; Kröncke, Thomas; Guckelberger, Olaf; Pape, Ulrich-Frank; Meier, Johannes; Thiel, Regina; Kivelitz, Dietmar; Sturm, Andreas; Hamm, Bernd; Röttgen, Rainer

2012-04-01

To evaluate fat saturated (fs) T2-weighted (w) fast relaxation fast spin echo (FRFSE)-sequences compared to the standard protocol with contrast agent for the evaluation of inflammatory activity in patients with Crohn's Disease (CD). Fourty-eight patients (male, 17; female, 33; mean age, 37 years) with suspicion of inflammatory activity in proven CD who underwent MR enteroclysis (MRE) at 1.5T (GE Healthcare) were retrospectively included. Two blinded radiologists analyzed MRE images for presence and extent of CD lesions and degree of local inflammation for fsT2-w FRFSE and contrast enhanced T1-w images (T2-activity; T1-activity; score, 1-4) in consensus. Furthermore, mural signal intensity (SI) ratios (T2-ratio; T1-ratio) were recorded. Patient based MRE findings were correlated with endoscopic (45 patients), surgical (6 patients), histopathological, and clinical data (CDAI) as a surrogate reference standard. In total, 24 of 48 eligible patients presented with acute inflammatory activity with 123 affected bowel segments. ROC analysis of the total inflammatory score presented an AUC of 0.93 (p<0.001) for T2-activity (T1-activity, AUC 0.63; p=0.019). ROC analysis revealed an AUC of 0.76 (p<0.001) for the T2-ratio (T1-ratio, AUC 0.51; p=0.93). General linear regression model revealed T2-activity (p=0.001) and age (p=0.024) as predictive factors of acute bowel inflammation. T2-w FRFSE-sequences can depict CD lesions and help to assess the inflammation activity, even with improved accuracy as compared to contrast-enhanced T1-w sequences. Copyright © 2011 European Crohn's and Colitis Organisation. Published by Elsevier B.V. All rights reserved.

Crystallography Coupled with Kinetic Analysis Provide Mechanistic Underpinnings of a Nicotine-Degrading Enzyme.

PubMed

Tararina, Margarita A; Xue, Song; Smith, Lauren C; Muellers, Samantha N; Miranda, Pedro O; Janda, Kim D; Allen, Karen N

2018-05-29

Nicotine oxidoreductase (NicA2) is a bacterial flavoenzyme, which catalyzes the first step of nicotine catabolism by oxidizing S-nicotine into N-methyl-myosmine. Its use has been proposed as a biotherapeutic for nicotine addiction due to its nanomolar substrate binding affinity. The first crystal structure of NicA2 has been reported, establishing NicA2 as a member of the monoamine oxidase (MAO) family. However, substrate specificity and structural determinants of substrate binding/catalysis have not been explored. Herein, analysis of pH-rate profile, single-turnover kinetics and binding data establish that pH does not significantly affect catalytic rate and product release is not rate limiting. The X-ray crystal structure of NicA2 with S-nicotine refined to 2.65 Å resolution reveals a hydrophobic binding site with a solvent exclusive cavity. Hydrophobic interactions predominantly orient the substrate, promoting the binding of a deprotonated species and supporting a hydride-transfer mechanism. Notably, NicA2 showed no activity against neurotransmitters oxidized by the two isoforms of human MAO. To further probe the substrate range of NicA2, enzyme activity was evaluated using a series of substrate analogs, indicating that S-nicotine is the optimal substrate and substitutions within the pyridyl ring abolish NicA2 activity. Moreover, mutagenesis and kinetic analysis of active-site residues reveal that removal of a hydrogen bond between the pyridyl ring of S-nicotine and the hydroxyl group of T381 has a 10-fold effect on KM, supporting the role of this bond in positioning the catalytically competent form of the substrate. Together, crystallography combined with kinetic analysis provide a deeper understanding of this enzyme's remarkable specificity.

Role of nitric oxide and antioxidant enzymes in the pathogenesis of oral cancer.

PubMed

Patel, Jayendrakumar B; Shah, Franky D; Shukla, Shilin N; Shah, Pankaj M; Patel, Prabhudas S

2009-01-01

Oral cancer is the leading malignancy in India. Nitric oxide and antioxidant enzymes play an important role in etiology of oral cancer. Therefore, the present study evaluates nitric oxide and antioxidant enzyme levels in healthy individual without tobacco habits (NHT, N=30) and healthy individuals with tobacco habits (WHT, n=90), patients with oral precancers (OPC, n=15) and oral cancer patients (n=126). Blood samples were collected from the subjects. NO2 + NO3 (nitrite+nitrate), superoxide dismutase (SOD) and catalase levels were estimated using highly specific spectrophotometeric methods. Statistical analysis was done by SPSS statistical software version 10. Mean plasma NO2 + NO3 levels were elevated in patients with OPC and oral cancer patients as compared to the controls. Mean activities of erythrocyte SOD and catalase were higher in WHT than NHT. Erythrocyte SOD and catalase levels were higher in WHT and patients with OPC as compared to NHT. The erythrocyte SOD and catalase activities were lower in oral cancer patients than patients with OPC. The erythrocyte SOD activity was higher in advanced oral cancer than the early disease. Erythrocyte catalase activity was lower in poorly differentiated tumors than well and moderately differentiated tumors. Pearson's correlation analysis revealed that alterations in plasma NO2 + NO3 levels were negatively associated with changes in erythrocyte SOD activities. The data revealed that the alterations in antioxidant activities were associated with production of nitric oxide in oral cancer, which may have significant role in oral carcinogenesis.

Aberrant neural processing of moral violations in criminal psychopaths

PubMed Central

Harenski, Carla L.; Harenski, Keith A.; Shane, Matthew S.; Kiehl, Kent A.

2010-01-01

A defining characteristic of psychopathy is the willingness to intentionally commit moral transgressions against others without guilt or remorse. Despite this ‘moral insensitivity’, the behavioral and neural correlates of moral decision-making in psychopathy have not been well studied. To address this issue, the authors used functional magnetic resonance imaging (fMRI) to record hemodynamic activity in 72 incarcerated male adults, stratified into psychopathic (N = 16) and nonpsychopathic (N = 16) groups based on scores from the Hare Psychopathy Checklist-Revised, while they made decisions regarding the ‘severity of moral violations’ of pictures that did or did not depict moral situations. Consistent with hypotheses, an analysis of brain activity during the evaluation of pictures depicting moral violations in psychopaths vs. nonpsychopaths showed atypical activity in several regions involved in moral decision-making. This included reduced moral/non-moral picture distinctions in the ventromedial prefrontal cortex and anterior temporal cortex in psychopaths relative to nonpsychopaths. In a separate analysis, the association between severity of moral violation ratings and brain activity across participants was compared in psychopaths versus nonpsychopaths. Results revealed a positive association between amygdala activity and severity ratings that was greater in nonpsychopaths than psychopaths, and a negative association between posterior temporal activity and severity ratings that was greater in psychopaths than nonpsychopaths. These results reveal potential neural underpinnings of moral insensitivity in psychopathy and are discussed with reference to neurobiological models of morality and psychopathy. PMID:21090881

Characterization and Expression Analysis of Receptor for Activated C Kinase from Silk-producing Insect Antheraea pernyi.

PubMed

Zhu, Bao-Jian; Yu, Hao; Tian, Sen; Dai, Li-Shang; Sun, Yu; Liu, Chao-Liang

2016-01-01

The receptor for activated C kinase (RACK) is an important scaffold protein with regulatory functions in cells. However, its role in the immune response of Antheraea pernyi to pathogen challenge remains unclear. To investigate the biological functions of RACK in the wild silkworm A. pernyi, cloning was performed and the expression patterns of the RACK gene were analyzed. Sequence analysis revealed that the RACK gene was 1120 bp containing a 960-bp open reading frame. The deduced RACK protein sequence reveals the higher identity with its homologs from other insects. SDS-PAGE and western blot analysis demonstrated successful expression of a 36-kDa recombinant RACK protein in Escherichia coli. The titer of a rabbit-raised antibody against recombinant RACK protein was about 1: 20000, determined by ELISA. Real-time PCR analysis showed that RACK expression was higher in fat bodies than in other examined A. pernyi tissues. The expression of RACK mRNA in fat bodies of fifth larvae of A. pernyi was obviously induced after nucleopolyhedrovirus, E. coli or Beauveria bassiana challenge. However, the expression patterns of RACK were different in response to these pathogens. Our data suggest that RACK may play a role in the innate immune responses of A. pernyi.

Novel Functional Properties of Drosophila CNS Glutamate Receptors

DOE Office of Scientific and Technical Information (OSTI.GOV)

Li, Yan; Dharkar, Poorva; Han, Tae-Hee

Phylogenetic analysis reveals AMPA, kainate, and NMDA receptor families in insect genomes, suggesting conserved functional properties corresponding to their vertebrate counterparts. However, heterologous expression of the Drosophila kainate receptor DKaiR1D and the AMPA receptor DGluR1A revealed novel ligand selectivity at odds with the classification used for vertebrate glutamate receptor ion channels (iGluRs). DKaiR1D forms a rapidly activating and desensitizing receptor that is inhibited by both NMDA and the NMDA receptor antagonist AP5; crystallization of the KaiR1D ligand-binding domain reveals that these ligands stabilize open cleft conformations, explaining their action as antagonists. Surprisingly, the AMPA receptor DGluR1A shows weak activation bymore » its namesake agonist AMPA and also by quisqualate. Crystallization of the DGluR1A ligand-binding domain reveals amino acid exchanges that interfere with binding of these ligands. The unexpected ligand-binding profiles of insect iGluRs allows classical tools to be used in novel approaches for the study of synaptic regulation.« less

Novel Functional Properties of Drosophila CNS Glutamate Receptors.

PubMed

Li, Yan; Dharkar, Poorva; Han, Tae-Hee; Serpe, Mihaela; Lee, Chi-Hon; Mayer, Mark L

2016-12-07

Phylogenetic analysis reveals AMPA, kainate, and NMDA receptor families in insect genomes, suggesting conserved functional properties corresponding to their vertebrate counterparts. However, heterologous expression of the Drosophila kainate receptor DKaiR1D and the AMPA receptor DGluR1A revealed novel ligand selectivity at odds with the classification used for vertebrate glutamate receptor ion channels (iGluRs). DKaiR1D forms a rapidly activating and desensitizing receptor that is inhibited by both NMDA and the NMDA receptor antagonist AP5; crystallization of the KaiR1D ligand-binding domain reveals that these ligands stabilize open cleft conformations, explaining their action as antagonists. Surprisingly, the AMPA receptor DGluR1A shows weak activation by its namesake agonist AMPA and also by quisqualate. Crystallization of the DGluR1A ligand-binding domain reveals amino acid exchanges that interfere with binding of these ligands. The unexpected ligand-binding profiles of insect iGluRs allows classical tools to be used in novel approaches for the study of synaptic regulation. VIDEO ABSTRACT. Published by Elsevier Inc.

Purification, developmental expression, and in silico characterization of α-amylase inhibitor from Echinochloa frumentacea.

PubMed

Panwar, Priyankar; Verma, A K; Dubey, Ashutosh

2018-05-01

Barnyard ( Echinochloa frumentacea ) and finger ( Eleusine coracana ) millet growing at northwestern Himalaya were explored for the α-amylase inhibitor (α-AI). The mature seeds of barnyard millet variety PRJ1 had maximum α-AI activity which increases in different developmental stage. α-AI was purified up to 22.25-fold from barnyard millet variety PRJ1. Semi-quantitative PCR of different developmental stages of barnyard millet seeds showed increased levels of the transcript from 7 to 28 days. Sequence analysis revealed that it contained 315 bp nucleotide which encodes 104 amino acid sequence with molecular weight 10.72 kDa. The predicted 3D structure of α-AI was 86.73% similar to a bifunctional inhibitor of ragi. In silico analysis of 71 α-AI protein sequences were carried out for biochemical features, homology search, multiple sequence alignment, phylogenetic tree construction, motif, and superfamily distribution of protein sequences. Analysis of multiple sequence alignment revealed the existence of conserved regions NPLP[S/G]CRWYVV[S/Q][Q/R]TCG[V/I] throughout sequences. Superfam analysis revealed that α-AI protein sequences were distributed among seven different superfamilies.

Allosteric mechanism of quinoline inhibitors for HIV RT-associated RNase with MD simulation and dynamics fluctuation network.

PubMed

Cai, Yi; Liu, Hao; Chen, Haifeng

2018-03-01

The human immunodeficiency virus (HIV) is a retrovirus which infects T lymphocyte of human body and causes immunodeficiency. Reverse transcriptase inhibitors (RTIs) can inhibit some functions of RT, preventing virus synthesis (double-stranded DNA), so that HIV virus replication can be reduced. Experimental results indicate a series of benzimidazole-based inhibitors which target HIV RT-associated RNase to inhibit the reverse transcription of HIV virus. However, the allosteric mechanism is still unclear. Here, molecular dynamics simulations and dynamics fluctuation network analysis were used to reveal the binding mode between the inhibitors and RT-associated RNase. The most active molecule has more hydrophobic and electrostatic interactions than the less active inhibitor. Dynamics correlation network analysis indicates that the most active inhibitor perturbs the network of RT-associated RNase and decreases the correlation of nodes. 3D-QSAR model suggests that two robust and reliable models were constructed and validated by independent test set. 3D-QSAR model also shows that bulky negatively charged or hydrophilic substituent is favorable to bioactivity. These results reveal the allosteric mechanism of quinoline inhibitors and help to improve the bioactivity. © 2017 John Wiley & Sons A/S.

Immunostimulatory activity of sulfated galactans isolated from the red seaweed Gracilaria fisheri and development of resistance against white spot syndrome virus (WSSV) in shrimp.

PubMed

Wongprasert, Kanokpan; Rudtanatip, Tawut; Praiboon, Jantana

2014-01-01

Sulfated galactans (SG) were isolated from the red seaweed Gracilaria fisheri (G. fisheri). Chemical analysis revealed SG contains sulfate (12.7%) and total carbohydrate (42.2%) with an estimated molecular mass of 100 kDa. Structure analysis by NMR and FT-IR spectroscopy revealed that SG is a complex structure with a linear backbone of alternating 3-linked β-D-galactopyranose and 4-linked 3,6-anhydrogalactose units with partial 6-O-methylate-β-D-galactopyranose and with sulfation occurring on C4 of D-galactopyranose and C6 of L-galactopyranose units. SG treatment enhanced immune parameters including total haemocytes, phenoloxidase activity, superoxide anions and superoxide dismutase in shrimp Penaeus monodon. Shrimp fed with Artemia salina enriched with SG (100 and 200 μg ml(-1)) and inoculated with white spot syndrome virus (WSSV) showed a significantly lower mortality rate and lower viral VP 28 amplification and expression than control. The results suggest that SG from G. fisheri exhibits immune stimulatory and antiviral activities that could protect P. monodon from WSSV infection. Copyright © 2013 Elsevier Ltd. All rights reserved.

Comparing anterior and posterior Hox complex formation reveals guidelines for predicting cis-regulatory elements

PubMed Central

Uhl, Juli D.; Cook, Tiffany A.; Gebelein, Brian

2010-01-01

Hox transcription factors specify numerous cell fates along the anterior-posterior axis by regulating the expression of downstream target genes. While expression analysis has uncovered large numbers of de-regulated genes in cells with altered Hox activity, determining which are direct versus indirect targets has remained a significant challenge. Here, we characterize the DNA binding activity of Hox transcription factor complexes on eight experimentally verified cis-regulatory elements. Hox factors regulate the activity of each element by forming protein complexes with two cofactor proteins, Extradenticle (Exd) and Homothorax (Hth). Using comparative DNA binding assays, we found that a number of flexible arrangements of Hox, Exd, and Hth binding sites mediate cooperative transcription factor complexes. Moreover, analysis of a Distal-less regulatory element (DMXR) that is repressed by abdominal Hox factors revealed that suboptimal binding sites can be combined to form high affinity transcription complexes. Lastly, we determined that the anterior Hox factors are more dependent upon Exd and Hth for complex formation than posterior Hox factors. Based upon these findings, we suggest a general set of guidelines to serve as a basis for designing bioinformatics algorithms aimed at identifying Hox regulatory elements using the wealth of recently sequenced genomes. PMID:20398649

A proteomic analysis reveals the interaction of GluK1 ionotropic kainate receptor subunits with Go proteins.

PubMed

Rutkowska-Wlodarczyk, Izabela; Aller, M Isabel; Valbuena, Sergio; Bologna, Jean-Charles; Prézeau, Laurent; Lerma, Juan

2015-04-01

Kainate receptors (KARs) are found ubiquitously in the CNS and are present presynaptically and postsynaptically regulating synaptic transmission and excitability. Functional studies have proven that KARs act as ion channels as well as potentially activating G-proteins, thus indicating the existance of a dual signaling system for KARs. Nevertheless, it is not clear how these ion channels activate G-proteins and which of the KAR subunits is involved. Here we performed a proteomic analysis to define proteins that interact with the C-terminal domain of GluK1 and we identified a variety of proteins with many different functions, including a Go α subunit. These interactions were verified through distinct in vitro and in vivo assays, and the activation of the Go protein by GluK1 was validated in bioluminescence resonance energy transfer experiments, while the specificity of this association was confirmed in GluK1-deficient mice. These data reveal components of the KAR interactome, and they show that GluK1 and Go proteins are natural partners, accounting for the metabotropic effects of KARs. Copyright © 2015 the authors 0270-6474/15/355171-09$15.00/0.

Mesoscale Variability in SUCCESS Data

NASA Technical Reports Server (NTRS)

Eckermann, Stephen D.; Stewart, Richard W. (Technical Monitor)

1998-01-01

Analysis of meteorological, chemical and microphysical data from the airborne SUCCESS (SUbsonic aircraft Contrail and Cloud Effects Special Study) mission is reported. Careful analysis of the complex DC-8 flight pattern of May 2, 1996 reveals 19 linear flight segments within six main geographical areas, which we have analyzed. Significant mountain wave activity is revealed in the data from the MMS (Meteorology Measurement System) and MTP (Microwave Temperature Profiler) instruments on the DC-8, which resembles previous observations of mountain wave structures near Boulder, Colorado. Strong mountain-wave-induced upwelling downwind of the Rockies is noted. Turbulence is also noted in regions of the mountain wave consistent with overturning near the tropopause. Zonal winds recorded on the ER-2 are shown to be consistent with mountain wave breaking at or near critical levels in the stratosphere, consistent with the strong turbulence reported by the pilot during the ER-2 flight. These observations have been supported with spectral analyses and modeling studies. 'Postcasts' of mountain wave activity on May 2, 1996 using the Naval Research Laboratory Mountain Wave Forecast Model predicts both strong mountain wave activity near the tropopause and strong mountain-wave-induced turbulence in the stratosphere.

Fermented guava leaf extract inhibits LPS-induced COX-2 and iNOS expression in Mouse macrophage cells by inhibition of transcription factor NF-kappaB.

PubMed

Choi, Soo-Youn; Hwang, Joon-Ho; Park, Soo-Young; Jin, Yeong-Jun; Ko, Hee-Chul; Moon, Sang-Wook; Kim, Se-Jae

2008-08-01

The goal of this study was to elucidate the antiinflammatory activities of Psidium guajava L. (guava) leaf. To improve the functionality of guava leaf, it was fermented with Phellinus linteus mycelia, Lactobacillus plantarum and Saccharomyces cerevisiae. The ethanol extract from fermented guava leaf inhibited lipopolysaccharide (LPS)-induced nitric oxide (NO) and prostaglandin E(2) (PGE(2)) production. Western blot analysis showed that fermented guava leaf extract decreased LPS-induced inducible nitric oxide synthase (iNOS) and the cyclooxygenase-2 (COX-2) protein level in RAW 264.7 cells. To investigate the mechanism involved, the study examined the effect of fermented guava leaf extract on LPS-induced nuclear factor-kappaB (NF-kappaB) activation. Fermented guava leaf extract significantly inhibited LPS-induced NF-kappaB transcriptional activity. Immunochemical analysis revealed that fermented guava leaf extract suppressed LPS-induced degradation of I-kappaBalpha. Taken together, the data indicate that fermented guava leaf extract is involved in the inhibition of iNOS and COX-2 via the down-regulation of NF-kappaB pathway, revealing a partial molecular basis for the antiinflammatory properties of fermented guava leaf extract.

Effect of a mirror-like illusion on activation in the precuneus assessed with functional near-infrared spectroscopy

NASA Astrophysics Data System (ADS)

Mehnert, Jan; Brunetti, Maddalena; Steinbrink, Jens; Niedeggen, Michael; Dohle, Christian

2013-06-01

Mirror therapy is a therapy to treat patients with pain syndromes or hemiparesis after stroke. However, the underlying neurophysiologic mechanisms are not clearly understood. In order to determine the effect of a mirror-like illusion (MIR) on brain activity using functional near-infrared spectroscopy, 20 healthy right-handed subjects were examined. A MIR was induced by a digital horizontal inversion of the subjects' filmed hand. Optodes were placed on the primary motor cortex (M1) and the occipito-parietal cortex (precuneus, PC). Regions of interest (ROI) were defined a priori based on previous results of similar studies and confirmed by the analysis of effect sizes. Analysis of variance of the ROI signal revealed a dissociated pattern: at the PC, the MIR caused a significant inversion of a hemispheric lateralization opposite to the perceived hand, independent of the moving hand. In contrast, activity in M1 showed lateralization opposite to the moving hand, but revealed no mirror effect. These findings extend our understanding on interhemispheric rivalry and indicate that a MIR is integrated into visuomotor coordination similar to normal view, irrespective of the hand that is actually performing the task.

Monitoring of bread cooling by statistical analysis of laser speckle patterns

NASA Astrophysics Data System (ADS)

Lyubenova, Tanya; Stoykova, Elena; Nacheva, Elena; Ivanov, Branimir; Panchev, Ivan; Sainov, Ventseslav

2013-03-01

The phenomenon of laser speckle can be used for detection and visualization of physical or biological activity in various objects (e.g. fruits, seeds, coatings) through statistical description of speckle dynamics. The paper presents the results of non-destructive monitoring of bread cooling by co-occurrence matrix and temporal structure function analysis of speckle patterns which have been recorded continuously within a few days. In total, 72960 and 39680 images were recorded and processed for two similar bread samples respectively. The experiments proved the expected steep decrease of activity related to the processes in the bread samples during the first several hours and revealed its oscillating character within the next few days. Characterization of activity over the bread sample surface was also obtained.

Evolution of structure and reactivity in a series of iconic carbenes.

PubMed

Zhang, Min; Moss, Robert A; Thompson, Jack; Krogh-Jespersen, Karsten

2012-01-20

We present experimental activation parameters for the reactions of six carbenes (CCl(2), CClF, CF(2), ClCOMe, FCOMe, and (MeO)(2)C) with six alkenes (tetramethylethylene, cyclohexene, 1-hexene, methyl acrylate, acrylonitrile, and α-chloroacrylonitrile). Activation energies range from -1 kcal/mol for the addition of CCl(2) to tetramethylethylene to 11 kcal/mol for the addition of FCOMe to acrylonitrile. A generally satisfactory analysis of major trends in the evolution of carbenic structure and reactivity is afforded by qualitative applications of frontier molecular orbital theory, although the observed entropies of activation appear to fall in a counterintuitive pattern. An analysis of computed cyclopropanation transition state parameters reveals significant nucleophilic selectivity of (MeO)(2)C toward α-chloroacrylonitrile.

An Integrated Proteomics and Bioinformatics Approach Reveals the Anti-inflammatory Mechanism of Carnosic Acid

PubMed Central

Wang, Li-Chao; Wei, Wen-Hui; Zhang, Xiao-Wen; Liu, Dan; Zeng, Ke-Wu; Tu, Peng-Fei

2018-01-01

Drastic macrophages activation triggered by exogenous infection or endogenous stresses is thought to be implicated in the pathogenesis of various inflammatory diseases. Carnosic acid (CA), a natural phenolic diterpene extracted from Salvia officinalis plant, has been reported to possess anti-inflammatory activity. However, its role in macrophages activation as well as potential molecular mechanism is largely unexplored. In the current study, we sought to elucidate the anti-inflammatory property of CA using an integrated approach based on unbiased proteomics and bioinformatics analysis. CA significantly inhibited the robust increase of nitric oxide and TNF-α, downregulated COX2 protein expression, and lowered the transcriptional level of inflammatory genes including Nos2, Tnfα, Cox2, and Mcp1 in LPS-stimulated RAW264.7 cells, a murine model of peritoneal macrophage cell line. The LC-MS/MS-based shotgun proteomics analysis showed CA negatively regulated 217 LPS-elicited proteins which were involved in multiple inflammatory processes including MAPK, nuclear factor (NF)-κB, and FoxO signaling pathways. A further molecular biology analysis revealed that CA effectually inactivated IKKβ/IκB-α/NF-κB, ERK/JNK/p38 MAPKs, and FoxO1/3 signaling pathways. Collectively, our findings demonstrated the role of CA in regulating inflammation response and provide some insights into the proteomics-guided pharmacological mechanism study of natural products. PMID:29713284

Functional analysis of the Arabidopsis PLDZ2 promoter reveals an evolutionarily conserved low-Pi-responsive transcriptional enhancer element

PubMed Central

Oropeza-Aburto, Araceli; Cruz-Ramírez, Alfredo; Acevedo-Hernández, Gustavo J.; Pérez-Torres, Claudia-Anahí; Caballero-Pérez, Juan; Herrera-Estrella, Luis

2012-01-01

Plants have evolved a plethora of responses to cope with phosphate (Pi) deficiency, including the transcriptional activation of a large set of genes. Among Pi-responsive genes, the expression of the Arabidopsis phospholipase DZ2 (PLDZ2) is activated to participate in the degradation of phospholipids in roots in order to release Pi to support other cellular activities. A deletion analysis was performed to identify the regions determining the strength, tissue-specific expression, and Pi responsiveness of this regulatory region. This study also reports the identification and characterization of a transcriptional enhancer element that is present in the PLDZ2 promoter and able to confer Pi responsiveness to a minimal, inactive 35S promoter. This enhancer also shares the cytokinin and sucrose responsive properties observed for the intact PLDZ2 promoter. The EZ2 element contains two P1BS motifs, each of which is the DNA binding site of transcription factor PHR1. Mutation analysis showed that the P1BS motifs present in EZ2 are necessary but not sufficient for the enhancer function, revealing the importance of adjacent sequences. The structural organization of EZ2 is conserved in the orthologous genes of at least eight families of rosids, suggesting that architectural features such as the distance between the two P1BS motifs are also important for the regulatory properties of this enhancer element. PMID:22210906

Endophytic Nocardiopsis sp. from Zingiber officinale with both antiphytopathogenic mechanisms and antibiofilm activity against clinical isolates.

PubMed

Sabu, Rohini; Soumya, K R; Radhakrishnan, E K

2017-06-01

Novel and potential antimicrobial compounds are essential to tackle the frequently emerging multidrug-resistant pathogens and also to develop environment friendly agricultural practices. In the current study, endophytic actinomycetes from rhizome of Zingiber officinale were explored in terms of its diversity and bioactive properties. Fourteen different organisms were isolated, identified and screened for activity against Pythium myriotylum and human clinical pathogens. Among these, Nocardiopsis sp. ZoA1 was found to have highest inhibition with excellent antibacterial effects compared to standard antibiotics. Remarkable antibiofilm property was also shown by the extract of ZoA1. Its antifungal activity against Pythium and other common phytopathogens was also found to be promising as confirmed by scanning electron microscopic analysis. By PCR-based sequence analysis of phz E gene, the organism was confirmed for the genetic basis of phenazine biosynthesis. Further GC-MS analysis of Nocardiopsis sp. revealed the presence of various compounds including Phenol, 2,4-bis (1,1-dimethylethyl) and trans cinnamic acid which can have significant role in the observed result. The current study is the first report on endophytic Nocardiopsis sp. from ginger with promising applications. In vivo treatment of Nocardiopsis sp. on ginger rhizome has revealed its inhibition towards the colonization of P. myriotylum which makes the study to have promises to manage the severe diseases in ginger like rhizome rot.

A Spiking Neural Network Methodology and System for Learning and Comparative Analysis of EEG Data From Healthy Versus Addiction Treated Versus Addiction Not Treated Subjects.

PubMed

Doborjeh, Maryam Gholami; Wang, Grace Y; Kasabov, Nikola K; Kydd, Robert; Russell, Bruce

2016-09-01

This paper introduces a method utilizing spiking neural networks (SNN) for learning, classification, and comparative analysis of brain data. As a case study, the method was applied to electroencephalography (EEG) data collected during a GO/NOGO cognitive task performed by untreated opiate addicts, those undergoing methadone maintenance treatment (MMT) for opiate dependence and a healthy control group. the method is based on an SNN architecture called NeuCube, trained on spatiotemporal EEG data. NeuCube was used to classify EEG data across subject groups and across GO versus NOGO trials, but also facilitated a deeper comparative analysis of the dynamic brain processes. This analysis results in a better understanding of human brain functioning across subject groups when performing a cognitive task. In terms of the EEG data classification, a NeuCube model obtained better results (the maximum obtained accuracy: 90.91%) when compared with traditional statistical and artificial intelligence methods (the maximum obtained accuracy: 50.55%). more importantly, new information about the effects of MMT on cognitive brain functions is revealed through the analysis of the SNN model connectivity and its dynamics. this paper presented a new method for EEG data modeling and revealed new knowledge on brain functions associated with mental activity which is different from the brain activity observed in a resting state of the same subjects.

RNA-Seq Analysis Reveals MAPKKK Family Members Related to Drought Tolerance in Maize

PubMed Central

Ren, Wen; Yang, Fengling; He, Hang; Zhao, Jiuran

2015-01-01

The mitogen-activated protein kinase (MAPK) cascade is an evolutionarily conserved signal transduction pathway that is involved in plant development and stress responses. As the first component of this phosphorelay cascade, mitogen-activated protein kinase kinase kinases (MAPKKKs) act as adaptors linking upstream signaling steps to the core MAPK cascade to promote the appropriate cellular responses; however, the functions of MAPKKKs in maize are unclear. Here, we identified 71 MAPKKK genes, of which 14 were novel, based on a computational analysis of the maize (Zea mays L.) genome. Using an RNA-seq analysis in the leaf, stem and root of maize under well-watered and drought-stress conditions, we identified 5,866 differentially expressed genes (DEGs), including 8 MAPKKK genes responsive to drought stress. Many of the DEGs were enriched in processes such as drought stress, abiotic stimulus, oxidation-reduction, and metabolic processes. The other way round, DEGs involved in processes such as oxidation, photosynthesis, and starch, proline, ethylene, and salicylic acid metabolism were clearly co-expressed with the MAPKKK genes. Furthermore, a quantitative real-time PCR (qRT-PCR) analysis was performed to assess the relative expression levels of MAPKKKs. Correlation analysis revealed that there was a significant correlation between expression levels of two MAPKKKs and relative biomass responsive to drought in 8 inbred lines. Our results indicate that MAPKKKs may have important regulatory functions in drought tolerance in maize. PMID:26599013

Twitter as a Potential Disaster Risk Reduction Tool. Part II: Descriptive Analysis of Identified Twitter Activity during the 2013 Hattiesburg F4 Tornado

PubMed Central

Cooper, Guy Paul; Yeager, Violet; Burkle, Frederick M.; Subbarao, Italo

2015-01-01

Background: This article describes a novel triangulation methodological approach for identifying twitter activity of regional active twitter users during the 2013 Hattiesburg EF-4 Tornado. Methodology: A data extraction and geographically centered filtration approach was utilized to generate Twitter data for 48 hrs pre- and post-Tornado. The data was further validated using six sigma approach utilizing GPS data. Results: The regional analysis revealed a total of 81,441 tweets, 10,646 Twitter users, 27,309 retweets and 2637 tweets with GPS coordinates. Conclusions: Twitter tweet activity increased 5 fold during the response to the Hattiesburg Tornado.  Retweeting activity increased 2.2 fold. Tweets with a hashtag increased 1.4 fold. Twitter was an effective disaster risk reduction tool for the Hattiesburg EF-4 Tornado 2013.  PMID:26203396

On the CCN (de)activation nonlinearities

NASA Astrophysics Data System (ADS)

Arabas, Sylwester; Shima, Shin-ichiro

2017-09-01

We take into consideration the evolution of particle size in a monodisperse aerosol population during activation and deactivation of cloud condensation nuclei (CCN). Our analysis reveals that the system undergoes a saddle-node bifurcation and a cusp catastrophe. The control parameters chosen for the analysis are the relative humidity and the particle concentration. An analytical estimate of the activation timescale is derived through estimation of the time spent in the saddle-node bifurcation bottleneck. Numerical integration of the system coupled with a simple air-parcel cloud model portrays two types of activation/deactivation hystereses: one associated with the kinetic limitations on droplet growth when the system is far from equilibrium, and one occurring close to equilibrium and associated with the cusp catastrophe. We discuss the presented analyses in context of the development of particle-based models of aerosol-cloud interactions in which activation and deactivation impose stringent time-resolution constraints on numerical integration.

Arsenic upregulates the expression of angiotensin II Type I receptor in mouse aortic endothelial cells.

PubMed

Hossain, Ekhtear; Ota, Akinobu; Takahashi, Miyuki; Karnan, Sivasundaram; Damdindorj, Lkhagvasuren; Konishi, Yuko; Konishi, Hiroyuki; Hosokawa, Yoshitaka

2013-06-20

Although chronic arsenic exposure is a well-known risk for cardiovascular disease and has a strong correlation with hypertension, the molecular pathogenesis underlying arsenic exposure-induced hypertension remains poorly understood. To delineate the pathogenesis, we examined changes in the mRNA levels of 2 angiotensin II Type I receptor (AT1R) subtypes, AT1AR and AT1BR, in a mouse aortic endothelial cell line, END-D. Quantitative real-time PCR analysis revealed significant increases in the mRNA levels of 2 AT1R subtypes, AT1AR and AT1BR following sodium arsenite (SA) treatment. Flow cytometry analysis revealed that SA increases the generation of reactive oxygen species (ROS) in a dose-dependent manner. In addition, western blot analysis revealed that SA enhances the phosphorylations of c-Jun N-terminal kinases (JNK) and activated protein 1 (AP-1). These phosphorylations were inhibited by N-acetylcysteine (NAC), an anti-oxidant. Finally, SA-induced AT1R expression was found to be prevented both by NAC and specific JNK inhibitor, SP6001325, strongly indicating that AT1R upregulation is a result of the ROS-mediated activation of the JNK signaling pathway. Taken together, our results indicate that arsenic indeed upregulates the AT1R expression, thus highlighting a role of arsenic-induced aberrant AT1R signaling in the pathogenesis of hypertension. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Regulation of the alpha-glucuronidase-encoding gene ( aguA) from Aspergillus niger.

PubMed

de Vries, R P; van de Vondervoort, P J I; Hendriks, L; van de Belt, M; Visser, J

2002-09-01

The alpha-glucuronidase gene aguA from Aspergillus niger was cloned and characterised. Analysis of the promoter region of aguA revealed the presence of four putative binding sites for the major carbon catabolite repressor protein CREA and one putative binding site for the transcriptional activator XLNR. In addition, a sequence motif was detected which differed only in the last nucleotide from the XLNR consensus site. A construct in which part of the aguA coding region was deleted still resulted in production of a stable mRNA upon transformation of A. niger. The putative XLNR binding sites and two of the putative CREA binding sites were mutated individually in this construct and the effects on expression were examined in A. niger transformants. Northern analysis of the transformants revealed that the consensus XLNR site is not actually functional in the aguA promoter, whereas the sequence that diverges from the consensus at a single position is functional. This indicates that XLNR is also able to bind to the sequence GGCTAG, and the XLNR binding site consensus should therefore be changed to GGCTAR. Both CREA sites are functional, indicating that CREA has a strong influence on aguA expression. A detailed expression analysis of aguA in four genetic backgrounds revealed a second regulatory system involved in activation of aguA gene expression. This system responds to the presence of glucuronic and galacturonic acids, and is not dependent on XLNR.

Physiological and Proteomics Analyses Reveal Low-Phosphorus Stress Affected the Regulation of Photosynthesis in Soybean.

PubMed

Chu, Shanshan; Li, Hongyan; Zhang, Xiangqian; Yu, Kaiye; Chao, Maoni; Han, Suoyi; Zhang, Dan

2018-06-06

Previous studies have revealed a significant genetic relationship between phosphorus (P)-efficiency and photosynthesis-related traits in soybean. In this study, we used proteome profiling in combination with expression analysis, biochemical investigations, and leaf ultrastructural analysis to identify the underlying physiological and molecular responses. The expression analysis and ultrastructural analysis showed that the photosynthesis key genes were decreased at transcript levels and the leaf mesophyll and chloroplast were severely damaged after low-P stress. Approximately 55 protein spots showed changes under low-P condition by mass spectrometry, of which 17 were involved in various photosynthetic processes. Further analysis revealed the depression of photosynthesis caused by low-P stress mainly involves the regulation of leaf structure, adenosine triphosphate (ATP) synthesis, absorption and transportation of CO₂, photosynthetic electron transport, production of assimilatory power, and levels of enzymes related to the Calvin cycle. In summary, our findings indicated that the existence of a stringent relationship between P supply and the genomic control of photosynthesis in soybean. As an important strategy to protect soybean photosynthesis, P could maintain the stability of cell structure, up-regulate the enzymes’ activities, recover the process of photosystem II (PSII), and induce the expression of low-P responsive genes and proteins.

Proteomics Analysis of Tissue Samples Reveals Changes in Mitochondrial Protein Levels in Parathyroid Hyperplasia over Adenoma

PubMed Central

AKPINAR, GURLER; KASAP, MURAT; CANTURK, NUH ZAFER; ZULFIGAROVA, MEHIN; ISLEK, EYLÜL ECE; GULER, SERTAC ATA; SIMSEK, TURGAY; CANTURK, ZEYNEP

2017-01-01

Background/Aim: To unveil the pathophysiology of primary hyperparathyroidism, molecular details of parathyroid hyperplasia and adenoma have to be revealed. Such details will provide the tools necessary for differentiation of these two look-alike diseases. Therefore, in the present study, a comparative proteomic study using postoperative tissue samples from the parathyroid adenoma and parathyroid hyperplasia patients was performed. Materials and Methods: Protein extracts were prepared from tissue samples (n=8 per group). Protein pools were created for each group and subjected to DIGE and conventional 2DE. Following image analysis, spots representing the differentially regulated proteins were excised from the and used for identification via MALDI-TOF/TOF analysis. Results: The identities of 40 differentially-expressed proteins were revealed. Fourteen of these proteins were over-expressed in the hyperplasia while 26 of them were over-expressed in the adenoma. Conclusion: Most proteins found to be over-expressed in the hyperplasia samples were mitochondrial, underlying the importance of the mitochondrial activity as a potential biomarker for differentiation of parathyroid hyperplasia from adenoma. PMID:28446534

Comparative analysis of Hibiscus sabdariffa (roselle) hot and cold extracts in respect to their potential for α-glucosidase inhibition.

PubMed

Rasheed, Dalia M; Porzel, Andrea; Frolov, Andrei; El Seedi, Hesham R; Wessjohann, Ludger A; Farag, Mohamed A

2018-06-01

Roselle (Hibiscus sabdariffa) is a functional food with potential health benefits, consumed either as hot or cold beverage. To ensure quality control of its various products, accurate measurement of active metabolites is warranted. Herein, we propose a combination of ultra-high performance liquid chromatography-mass spectrometry (UHPLC-MS) and nuclear magnetic resonance (NMR) analytical platforms for the untargeted characterization of metabolites in two roselle cultivars, Aswan and Sudan-1. The analyses revealed 33 metabolites, including sugars, flavonoids, anthocyanins, phenolic and aliphatic organic acids. Their relative contents in cultivars were assessed via principle component analysis (PCA) and orthogonal projection to latent structures analysis (OPLS). Impact of the different extraction methods (decoction, infusion and maceration) was compared by quantitative 1 H NMR spectroscopy, revealing cold maceration to be optimal for preserving anthocyanins, whereas infusion was more suited for recovering organic acids. The metabolite pattern revealed by the different extraction methods was found in good correlation for their ability to inhibit α-glucosidase enzyme. Copyright © 2018 Elsevier Ltd. All rights reserved.

Combined venomics, antivenomics and venom gland transcriptome analysis of the monocoled cobra (Naja kaouthia) from China.

PubMed

Xu, Ning; Zhao, Hong-Yan; Yin, Yin; Shen, Shan-Shan; Shan, Lin-Lin; Chen, Chuan-Xi; Zhang, Yan-Xia; Gao, Jian-Fang; Ji, Xiang

2017-04-21

We conducted an omics-analysis of the venom of Naja kaouthia from China. Proteomics analysis revealed six protein families [three-finger toxins (3-FTx), phospholipase A 2 (PLA 2 ), nerve growth factor, snake venom metalloproteinase (SVMP), cysteine-rich secretory protein and ohanin], and venom-gland transcriptomics analysis revealed 28 protein families from 79 unigenes. 3-FTx (56.5% in proteome/82.0% in transcriptome) and PLA 2 (26.9%/13.6%) were identified as the most abundant families in venom proteome and venom-gland transcriptome. Furthermore, N. kaouthia venom expressed strong lethality (i.p. LD 50 : 0.79μg/g) and myotoxicity (CK: 5939U/l) in mice, and showed notable activity in PLA 2 but weak activity in SVMP, l-amino acid oxidase or 5' nucleotidase. Antivenomic assessment revealed that several venom components (nearly 17.5% of total venom) from N. kaouthia could not be thoroughly immunocaptured by commercial Naja atra antivenom. ELISA analysis revealed that there was no difference in the cross-reaction between N. kaouthia and N. atra venoms against the N. atra antivenom. The use of commercial N. atra antivenom in treatment of snakebites caused by N. kaouthia is reasonable, but design of novel antivenom with the attention on enhancing the immune response of non-immunocaptured components should be encouraged. The venomics, antivenomics and venom-gland transcriptome of the monocoled cobra (Naja kaouthia) from China have been elucidated. Quantitative and qualitative differences are evident when venom proteomic and venom-gland transcriptomic profiles are compared. Two protein families (3-FTx and PLA 2 ) are found to be the predominated components in N. kaouthia venom, and considered as the major players in functional role of venom. Other protein families with relatively low abundance appear to be minor in the functional significance. Antivenomics and ELISA evaluation reveal that the N. kaouthia venom can be effectively immunorecognized by commercial N. atra antivenom, but still a small number of venom components could not be thoroughly immunocaptured. The findings indicate that exploring the precise composition of snake venom should be executed by an integrated omics-approach, and elucidating the venom composition is helpful in understanding composition-function relationships and will facilitate the clinical application of antivenoms. Copyright © 2017 Elsevier B.V. All rights reserved.

Analysis of slow-wave activity and slow-wave oscillations prior to somnambulism.

PubMed

Jaar, Olivier; Pilon, Mathieu; Carrier, Julie; Montplaisir, Jacques; Zadra, Antonio

2010-11-01

STUDY OBJECTIVIES: several studies have investigated slow wave sleep EEG parameters, including slow-wave activity (SWA) in relation to somnambulism, but results have been both inconsistent and contradictory. The first goal of the present study was to conduct a quantitative analysis of sleepwalkers' sleep EEG by studying fluctuations in spectral power for delta (1-4 Hz) and slow delta (0.5-1 Hz) before the onset of somnambulistic episodes. A secondary aim was to detect slow-wave oscillations to examine changes in their amplitude and density prior to behavioral episodes. twenty-two adult sleepwalkers were investigated polysomnographically following 25 h of sleep deprivation. analysis of patients' sleep EEG over the 200 sec prior to the episodes' onset revealed that the episodes were not preceded by a gradual increase in spectral power for either delta or slow delta over frontal, central, or parietal leads. However, time course comparisons revealed significant changes in the density of slow-wave oscillations as well as in very slow oscillations with significant increases occurring during the final 20 sec immediately preceding episode onset. the specificity of these sleep EEG parameters for the occurrence and diagnosis of NREM parasomnias remains to be determined.

Functional network connectivity analysis based on partial correlation in Alzheimer's disease

NASA Astrophysics Data System (ADS)

Zhang, Nan; Guan, Xiaoting; Zhang, Yumei; Li, Jingjing; Chen, Hongyan; Chen, Kewei; Fleisher, Adam; Yao, Li; Wu, Xia

2009-02-01

Functional network connectivity (FNC) measures the temporal dependency among the time courses of functional networks. However, the marginal correlation between two networks used in the classic FNC analysis approach doesn't separate the FNC from the direct/indirect effects of other networks. In this study, we proposed an alternative approach based on partial correlation to evaluate the FNC, since partial correlation based FNC can reveal the direct interaction between a pair of networks, removing dependencies or influences from others. Previous studies have demonstrated less task-specific activation and less rest-state activity in Alzheimer's disease (AD). We applied present approach to contrast FNC differences of resting state network (RSN) between AD and normal controls (NC). The fMRI data under resting condition were collected from 15 AD and 16 NC. FNC was calculated for each pair of six RSNs identified using Group ICA, thus resulting in 15 (2 out of 6) pairs for each subject. Partial correlation based FNC analysis indicated 6 pairs significant differences between groups, while marginal correlation only revealed 2 pairs (involved in the partial correlation results). Additionally, patients showed lower correlation than controls among most of the FNC differences. Our results provide new evidences for the disconnection hypothesis in AD.

A framework of knowledge creation processes in participatory simulation of hospital work systems.

PubMed

Andersen, Simone Nyholm; Broberg, Ole

2017-04-01

Participatory simulation (PS) is a method to involve workers in simulating and designing their own future work system. Existing PS studies have focused on analysing the outcome, and minimal attention has been devoted to the process of creating this outcome. In order to study this process, we suggest applying a knowledge creation perspective. The aim of this study was to develop a framework describing the process of how ergonomics knowledge is created in PS. Video recordings from three projects applying PS of hospital work systems constituted the foundation of process mining analysis. The analysis resulted in a framework revealing the sources of ergonomics knowledge creation as sequential relationships between the activities of simulation participants sharing work experiences; experimenting with scenarios; and reflecting on ergonomics consequences. We argue that this framework reveals the hidden steps of PS that are essential when planning and facilitating PS that aims at designing work systems. Practitioner Summary: When facilitating participatory simulation (PS) in work system design, achieving an understanding of the PS process is essential. By applying a knowledge creation perspective and process mining, we investigated the knowledge-creating activities constituting the PS process. The analysis resulted in a framework of the knowledge-creating process in PS.

Granular activated carbon for removal of organic matter and turbidity from secondary wastewater.

PubMed

Hatt, J W; Germain, E; Judd, S J

2013-01-01

A range of commercial granular activated carbon (GAC) media have been assessed as pretreatment technologies for a downstream microfiltration (MF) process. Media were assessed on the basis of reduction in both organic matter and turbidity, since these are known to cause fouling in MF membranes. Isotherm adsorption analysis through jar testing with supplementary column trials revealed a wide variation between the different adsorbent materials with regard to organics removal and adsorption kinetics. Comparison with previous work using powdered activated carbon (PAC) revealed that for organic removal above 60% the use of GAC media incurs a significantly lower carbon usage rate than PAC. All GACs tested achieved a minimum of 80% turbidity removal. This combination of turbidity and organic removal suggests that GAC would be expected to provide a significant reduction in fouling of a downstream MF process with improved product water quality.

Complexity of EEG-signal in Time Domain - Possible Biomedical Application

NASA Astrophysics Data System (ADS)

Klonowski, Wlodzimierz; Olejarczyk, Elzbieta; Stepien, Robert

2002-07-01

Human brain is a highly complex nonlinear system. So it is not surprising that in analysis of EEG-signal, which represents overall activity of the brain, the methods of Nonlinear Dynamics (or Chaos Theory as it is commonly called) can be used. Even if the signal is not chaotic these methods are a motivating tool to explore changes in brain activity due to different functional activation states, e.g. different sleep stages, or to applied therapy, e.g. exposure to chemical agents (drugs) and physical factors (light, magnetic field). The methods supplied by Nonlinear Dynamics reveal signal characteristics that are not revealed by linear methods like FFT. Better understanding of principles that govern dynamics and complexity of EEG-signal can help to find `the signatures' of different physiological and pathological states of human brain, quantitative characteristics that may find applications in medical diagnostics.

Functional-anatomic correlates of individual differences in memory.

PubMed

Kirchhoff, Brenda A; Buckner, Randy L

2006-07-20

Memory abilities differ greatly across individuals. To explore a source of these differences, we characterized the varied strategies people adopt during unconstrained encoding. Participants intentionally encoded object pairs during functional MRI. Principal components analysis applied to a strategy questionnaire revealed that participants variably used four main strategies to aid learning. Individuals' use of verbal elaboration and visual inspection strategies independently correlated with their memory performance. Verbal elaboration correlated with activity in a network of regions that included prefrontal regions associated with controlled verbal processing, while visual inspection correlated with activity in a network of regions that included an extrastriate region associated with object processing. Activity in regions associated with use of these strategies was also correlated with memory performance. This study reveals functional-anatomic correlates of verbal and perceptual strategies that are variably used by individuals during encoding. These strategies engage distinct brain regions and may separately influence memory performance.

The Neurobiological Grounding of Persistent Stuttering: from Structure to Function.

PubMed

Neef, Nicole E; Anwander, Alfred; Friederici, Angela D

2015-09-01

Neuroimaging and transcranial magnetic stimulation provide insights into the neuronal mechanisms underlying speech disfluencies in chronic persistent stuttering. In the present paper, the goal is not to provide an exhaustive review of existing literature, but rather to highlight robust findings. We, therefore, conducted a meta-analysis of diffusion tensor imaging studies which have recently implicated disrupted white matter connectivity in stuttering. A reduction of fractional anisotropy in persistent stuttering has been reported at several different loci. Our meta-analysis revealed consistent deficits in the left dorsal stream and in the interhemispheric connections between the sensorimotor cortices. In addition, recent fMRI meta-analyses link stuttering to reduced left fronto-parieto-temporal activation while greater fluency is associated with boosted co-activations of right fronto-parieto-temporal areas. However, the physiological foundation of these irregularities is not accessible with MRI. Complementary, transcranial magnetic stimulation (TMS) reveals local excitatory and inhibitory regulation of cortical dynamics. Applied to a speech motor area, TMS revealed reduced speech-planning-related neuronal dynamics at the level of the primary motor cortex in stuttering. Together, this review provides a focused view of the neurobiology of stuttering to date and may guide the rational design of future research. This future needs to account for the perpetual dynamic interactions between auditory, somatosensory, and speech motor circuits that shape fluent speech.

Pervasive competition between threat and reward in the brain.

PubMed

Choi, Jong Moon; Padmala, Srikanth; Spechler, Philip; Pessoa, Luiz

2014-06-01

In the current functional MRI study, we investigated interactions between reward and threat processing. Visual cues at the start of each trial informed participants about the chance of winning monetary reward and/or receiving a mild aversive shock. We tested two competing hypothesis: according to the 'salience hypothesis', in the condition involving both reward and threat, enhanced activation would be observed because of increased salience; according to the 'competition hypothesis', the processing of reward and threat would trade-off against each other, leading to reduced activation. Analysis of skin conductance data during a delay phase revealed an interaction between reward and threat processing, such that the effect of reward was reduced during threat and the effect of threat was reduced during reward. Analysis of imaging data during the same task phase revealed interactions between reward and threat processing in several regions, including the midbrain/ventral tegmental area, caudate, putamen, bed nucleus of the stria terminalis, anterior insula, middle frontal gyrus and dorsal anterior cingulate cortex. Taken together, our findings reveal conditions during which reward and threat trade-off against each other across multiple sites. Such interactions are suggestive of competitive processes and may reflect the organization of opponent systems in the brain. © The Author (2013). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

Acquired resistance of EGFR-mutant lung adenocarcinomas to afatinib plus cetuximab is associated with activation of mTORC1

PubMed Central

Pirazzoli, Valentina; Nebhan, Caroline; Song, Xiaoling; Wurtz, Anna; Walther, Zenta; Cai, Guoping; Zhao, Zhongming; Jia, Peilin; de Stanchina, Elisa; Shapiro, Erik M.; Gale, Molly; Yin, Ruonan; Horn, Leora; Carbone, David P.; Stephens, Philip J; Miller, Vincent; Gettinger, Scott; Pao, William; Politi, Katerina

2014-01-01

SUMMARY Patients with EGFR-mutant lung adenocarcinomas (LUADs) who initially respond to first-generation TKIs develop resistance to these drugs. A combination of the irreversible TKI afatinib and the EGFR antibody cetuximab can be used to overcome resistance to first-generation TKIs; however, resistance to this drug combination eventually emerges. We identified activation of the mTORC1 signaling pathway as a mechanism of resistance to dual inhibition of EGFR in mouse models. Addition of rapamycin reversed resistance in vivo. Analysis of afatinib+cetuximab-resistant biopsy specimens revealed the presence of genomic alterations in genes that modulate mTORC1 signaling including NF2 and TSC1. These findings pinpoint enhanced mTORC1 activation as a mechanism of resistance to afatinib+cetuximab and identify genomic mechanisms that lead to activation of this pathway, revealing a potential therapeutic strategy for treating patients with resistance to these drugs. PMID:24813888

Retrotransposon Tf1 is targeted to pol II promoters by transcription activators

PubMed Central

Leem, Young-Eun; Ripmaster, Tracy; Kelly, Felice; Ebina, Hirotaka; Heincelman, Marc; Zhang, Ke; Grewal, Shiv I. S.; Hoffman, Charles S.; Levin, Henry L.

2008-01-01

SUMMARY The LTR-retrotransposon Tf1 preserves the coding capacity of its host Schizosaccharomyces pombe by integrating upstream of open reading frames (ORFs). To determine which features of the target sites were recognized by the transposon, we introduced plasmids containing candidate insertion sites into S. pombe and mapped the positions of integration. We found that Tf1 was targeted specifically to the promoters of pol II transcribed genes. A detailed analysis of integration in plasmids that contained either ade6 or fbp1 revealed insertions occurred in the promoters at positions where transcription factors bound. Further experiments revealed that the activator Atf1p and its binding site were required for directing integration to the promoter of fbp1. An interaction between Tf1 integrase and Atf1p was observed indicating that integration at fbp1 was mediated by the activator bound to its promoter. Surprisingly we found Tf1 contained sequences that activated transcription and these substituted for elements of the ade6 promoter disrupted by integration. PMID:18406330

Retrotransposon Tf1 is targeted to Pol II promoters by transcription activators.

PubMed

Leem, Young-Eun; Ripmaster, Tracy L; Kelly, Felice D; Ebina, Hirotaka; Heincelman, Marc E; Zhang, Ke; Grewal, Shiv I S; Hoffman, Charles S; Levin, Henry L

2008-04-11

The LTR-retrotransposon Tf1 preserves the coding capacity of its host Schizosaccharomyces pombe by integrating upstream of open reading frames (ORFs). To determine which features of the target sites were recognized by the transposon, we introduced plasmids containing candidate insertion sites into S. pombe and mapped the positions of integration. We found that Tf1 was targeted specifically to the promoters of Pol II-transcribed genes. A detailed analysis of integration in plasmids that contained either ade6 or fbp1 revealed insertions occurred in the promoters at positions where transcription factors bound. Further experiments revealed that the activator Atf1p and its binding site were required for directing integration to the promoter of fbp1. An interaction between Tf1 integrase and Atf1p was observed, indicating that integration at fbp1 was mediated by the activator bound to its promoter. Surprisingly, we found Tf1 contained sequences that activated transcription, and these substituted for elements of the ade6 promoter disrupted by integration.

[A DNA study of rat liver oligonucleosomes enriched by transcriptionally active genes during induction due to the administration of an amino acid mixture].

PubMed

Vardevanian, P O; Davtian, A M; Tiratsuian, S G; Vardevanian, A O

1990-01-01

A highly active fraction of rat liver oligonucleosome DNA has been isolated and studied by means of thermal denaturation after induction by amino acid mixture or hydrocortisone. A considerable redistribution of DNA content has been shown in sucrose gradient fractions during these forms of induction. The changes are revealed in melting temperature, differential melting profile of DNA, isolated from actively transcribed chromatine fractions. Analysis of melting profiles shows changes of GC content of oligonucleosome DNA, suggesting that there are differences in activation during two studied forms of induction.

[Insect cholinesterases and irreversible inhibitors. Statistical treatment of the data].

PubMed

Moralev, S N

2010-01-01

The data on sensitivity of cholinesterases (ChE) of different insects to reversible inhibitors, as well as the data on physico-chemical parameters of amino acids constituting their active centers, were treated by factor analysis and juxtaposed. It is shown that both these characteristics are related to taxonomical belonging of insects. It is revealed the "material substrate" of the factors determining inhibitor action specificity, which are specific sites in ChE active center.

Structure of the c-Ki-ras gene in a rat fibrosarcoma induced by 1,8-dinitropyrene.

PubMed Central

Tahira, T; Hayashi, K; Ochiai, M; Tsuchida, N; Nagao, M; Sugimura, T

1986-01-01

Restriction enzyme maps were made of the region around exons 1 and 2 of activated c-Ki-ras of a fibrosarcoma (1,8-DNP2) induced in a rat by 1,8-dinitropyrene. Nucleotide sequence analysis revealed that activated c-Ki-ras shows a G----T transversion in codon 12 and consequently encodes cysteine instead of glycine in normal rat c-Ki-ras. PMID:3023884

Synthesis, characterization and anti-microbial evaluation of Cu(II), Ni(II), Pt(II) and Pd(II) sulfonylhydrazone complexes; 2D-QSAR analysis of Ni(II) complexes of sulfonylhydrazone derivatives

NASA Astrophysics Data System (ADS)

Özbek, Neslihan; Alyar, Saliha; Alyar, Hamit; Şahin, Ertan; Karacan, Nurcan

2013-05-01

Copper(II), nickel(II), platinum(II) and palladium(II) complexes with 2-hydroxy-1-naphthaldehyde-N-methylpropanesulfonylhydrazone (nafpsmh) derived from propanesulfonic acid-1-methylhydrazide (psmh) were synthesized, their structure were identified, and antimicrobial activity of the compounds was screened against three Gram-positive and three Gram-negative bacteria. The results of antimicrobial studies indicate that Pt(II) and Pd(II) complexes showed the most activity against all bacteria. The crystal structure of 2-hydroxy-1-naphthaldehyde-N-methylpropanesulfonylhydrazone (nafpsmh) was also investigated by X-ray analysis. A series of Ni(II) sulfonyl hydrazone complexes (1-33) was synthesized and tested in vitro against Escherichia coli and Staphylococcus aureus. Their antimicrobial activities were used in the QSAR analysis. Four-parameter QSAR models revealed that nucleophilic reaction index for Ni and O atoms, and HOMO-LUMO energy gap play key roles in the antimicrobial activity.

Increased spatial granularity of left brain activation and unique age/gender signatures: a 4D frequency domain approach to cerebral lateralization at rest.

PubMed

Agcaoglu, O; Miller, R; Mayer, A R; Hugdahl, K; Calhoun, V D

2016-12-01

Cerebral lateralization is a well-studied topic. However, most of the research to date in functional magnetic resonance imaging (fMRI) has been carried out on hemodynamic fluctuations of voxels, networks, or regions of interest (ROIs). For example, cerebral differences can be revealed by comparing the temporal activation of an ROI in one hemisphere with the corresponding homotopic region in the other hemisphere. While this approach can reveal significant information about cerebral organization, it does not provide information about the full spatiotemporal organization of the hemispheres. The cerebral differences revealed in literature suggest that hemispheres have different spatiotemporal organization in the resting state. In this study, we evaluate cerebral lateralization in the 4D spatiotemporal frequency domain to compare the hemispheres in the context of general activation patterns at different spatial and temporal scales. We use a gender-balanced resting fMRI dataset comprising over 600 healthy subjects ranging in age from 12 to 71, that have previously been studied with a network specific voxel-wise and global analysis of lateralization (Agcaoglu, et al. NeuroImage, 2014). Our analysis elucidates significant differences in the spatiotemporal organization of brain activity between hemispheres, and generally more spatiotemporal fluctuation in the left hemisphere especially in the high spatial frequency bands, and more power in the right hemisphere in the low and middle spatial frequencies. Importantly, the identified effects are not visible in the context of a typical assessment of voxelwise, regional, or even global laterality, thus our study highlights the value of 4D spatiotemporal frequency domain analyses as a complementary and powerful tool for studying brain function.

Endo-symbiont mediated synthesis of gold nanobactericides and their activity against human pathogenic bacteria.

PubMed

Syed, Baker; M N, Nagendra Prasad; K, Mohan Kumar; B L, Dhananjaya; Satish, Sreedharamurthy

2017-06-01

Synthesis of gold nanobactericides (AuNBs) were achieved by treating 1mM chloroaurate with cell free supernatant of Aneurinibacillus migulanus. Formation of AuNBs was initially was monitored with change in colour to ruby red. Further confirmation was assessed with UV-visible spectra with maximum absorption occurring at 510nm. Transmission electron microscopy (TEM) analysis revealed the polydispersity of AuNBs with size distribution ranging from 10 to 60nm with an average size of 30nm. Crystalline nature was studied using X-ray diffraction which exhibited characteristic peaks indexed to Bragg's reflection at 2θ angle which confers (111), (200), (220), and (311) planes suggesting AuNBs were face-centred cubic. Fourier transform infrared spectroscopy (FTIR) analysis revealed absorption peaks occurring at 3341cm -1 , 1635cm -1 and 670cm -1 which corresponds to functional groups attributing to synthesis. The antibacterial efficacy of AuNBs was tested against selective human pathogenic bacteria and activity was measured as zone of inhibition by using disc and well diffusion. Bactericidal activity was interpreted with standard antibiotics gentamicin and kanamycin. Micro broth dilution assay expressed the minimal concentration of AuNBs to inhibit the growth of test pathogens. Highest activity was observed against Pseudomonas aeruginosa (MTCC 7903) with 21.00±0.57mm compared to other pathogens. The possible mode of action of AuNBs on DNA was carried out with in vitro assay as preliminary test against pathogenic DNA isolated from P. aeruginosa. Further studies will be interesting enough to reveal the exact interactive mechanism of AuNBs with DNA. Overall study contributes towards biogenic synthesis of AuNBs as one of the alternative in combating drug resistant pathogens. Copyright © 2017 Elsevier B.V. All rights reserved.

Mycobacterium paratuberculosis, Mycobacterium smegmatis, and lipopolysaccharide induce different transcriptional and post-transcriptional regulation of the IRG1 gene in murine macrophages.

PubMed

Basler, Tina; Jeckstadt, Sabine; Valentin-Weigand, Peter; Goethe, Ralph

2006-03-01

Mycobacterium avium subspecies paratuberculosis (MAP) causes a chronic enteritis in ruminants. In addition, MAP is presently the most favored pathogen linked to Crohn's disease. In this study, we were interested in dissecting the molecular mechanisms of macrophage activation or deactivation after infection with MAP. By subtractive hybridization of cDNAs, we identified the immune-responsive gene 1 (IRG1), which was expressed substantially higher in lipopolysaccharide (LPS)-stimulated than in MAP-infected murine macrophage cell lines. A nuclear run-on transcription assay revealed that the IRG1 gene was activated transcriptionally in LPS-stimulated and MAP-infected macrophages with higher expression in LPS-stimulated cells. Analysis of post-transcriptional regulation demonstrated that IRG1 mRNA stability was increased in LPS-stimulated but not in MAP-infected macrophages. Furthermore, IRG1 gene expression of macrophages infected with the nonpathogenic Mycobacterium smegmatis differed from those of LPS-stimulated and MAP-infected macrophages. At 2 h postinfection, M. smegmatis-induced IRG1 gene expression was as low as in MAP-infected, and 8 h postinfection, it increased nearly to the level in LPS-stimulated macrophages. Transient transfection experiments revealed similar IRG1 promoter activities in MAP- and M. smegmatis-infected cells. Northern analysis demonstrated increased IRG1 mRNA stability in M. smegmatis-infected macrophages. IRG1 mRNA stabilization was p38 mitogen-activated protein kinase-independent. Inhibition of protein synthesis revealed that constitutively expressed factors seemed to be responsible for IRG1 mRNA destabilization. Thus, our data demonstrate that transcriptional and post-transcriptional mechanisms are responsible for a differential IRG1 gene expression in murine macrophages treated with LPS, MAP, and M. smegmatis.

Traditional medicines used by Q'eqchi' Maya to treat diabetic symptoms and their antiglycation potential.

PubMed

Ferrier, J; Saleem, A; Carter Ramirez, A; Liu, R; Chen, Eric; Pesek, T; Cal, V; Balick, M; Arnason, J T

2018-06-21

Because of the recent increase in type 2 diabetes and the need for complementary treatments in remote communities in many parts of the world, we undertook a study of treatments for diabetic symptoms used by traditional Q'eqchi' Maya healers of Belize. We used quantitative ethnobotany to rank culturally important taxa and subsequent pharmacological and phytochemical studies to assess bioactivity. Antidiabetic plants identified in field interviews with traditional healers were ranked by syndromic importance value (SIV) based on 15 symptoms of diabetes.. Species ranked with high SIV were tested in an assay relevant to many diabetes complications, the advanced glycation endproduct (AGE) inhibition assay. Active principles were identified by phytochemical analysis and bioassay. We collected over 70 plant species having a promising SIV score. The plants represented a broad range of neotropical taxa. Selected Q'eqchi' antidiabetic plants with high SIV were collected in bulk and tested in the advanced glycation endproduct (AGE) inhibition assay. All plant extracts showed AGE inhibition and the half maximal inhibitory concentration (IC 50 ) ranged from 40.8 to 733µg/mL, while the most active species was Tynanthus guatemalensis Donn (Bignoniaceae). A linear regression showed a significant relationship between 1/ IC 50 and SIV. Phytochemical analysis revealed the presence of verbascoside, as a major component and active principle of the T guatemalensis which had an IC 50 = 5.1µg/mL, comparable to the positive control quercetin. The results reveal a rich botanical tradition of antidiabetic symptom treatments among the Q'eqchi'. Study of highly ranked plants revealed their activity in AGE inhibition correlated with SIV. T. guatemalensis was identified as a promising species for further evaluation and local use. Copyright © 2018. Published by Elsevier B.V.

Multiple determinants controlling activation of yeast replication origins late in S phase.

PubMed

Friedman, K L; Diller, J D; Ferguson, B M; Nyland, S V; Brewer, B J; Fangman, W L

1996-07-01

Analysis of a 131-kb segment of the left arm of yeast chromosome XIV beginning 157 kb from the telomere reveals four highly active origins of replication that initiate replication late in S phase. Previous work has shown that telomeres act as determinants for late origin activation. However, at least two of the chromosome XIV origins maintain their late activation time when located on large circular plasmids, indicating that late replication is independent of telomeres. Analysis of the replication time of plasmid derivatives containing varying amounts of chromosome XIV DNA show that a minimum of three chromosomal elements, distinct from each tested origin, contribute to late activation time. These late determinants are functionally equivalent, because duplication of one set of contributing sequences can compensate for the removal of another set. Furthermore, insertion of an origin that is normally early activated into this domain results in a shift to late activation, suggesting that the chromosome XIV origins are not unique in their ability to respond to the late determinants.

The Peroxisome Proliferator-Activated Receptor α is dispensable for cold-induced adipose tissue browning in mice.

PubMed

Defour, Merel; Dijk, Wieneke; Ruppert, Philip; Nascimento, Emmani B M; Schrauwen, Patrick; Kersten, Sander

2018-04-01

Chronic cold exposure causes white adipose tissue (WAT) to adopt features of brown adipose tissue (BAT), a process known as browning. Previous studies have hinted at a possible role for the transcription factor Peroxisome Proliferator-Activated Receptor alpha (PPARα) in cold-induced browning. Here we aimed to investigate the importance of PPARα in driving transcriptional changes during cold-induced browning in mice. Male wildtype and PPARα-/- mice were housed at thermoneutrality (28 °C) or cold (5 °C) for 10 days. Whole genome expression analysis was performed on inguinal WAT. In addition, other analyses were carried out. Whole genome expression data of livers of wildtype and PPARα-/- mice fasted for 24 h served as positive control for PPARα-dependent gene regulation. Cold exposure increased food intake and decreased weight of BAT and WAT to a similar extent in wildtype and PPARα-/- mice. Except for plasma non-esterified fatty acids, none of the cold-induced changes in plasma metabolites were dependent on PPARα genotype. Histological analysis of inguinal WAT showed clear browning upon cold exposure but did not reveal any morphological differences between wildtype and PPARα-/- mice. Transcriptomics analysis of inguinal WAT showed a marked effect of cold on overall gene expression, as revealed by principle component analysis and hierarchical clustering. However, wildtype and PPARα-/- mice clustered together, even after cold exposure, indicating a similar overall gene expression profile in the two genotypes. Pathway analysis revealed that cold upregulated pathways involved in energy usage, oxidative phosphorylation, and fatty acid β-oxidation to a similar extent in wildtype and PPARα-/- mice. Furthermore, cold-mediated induction of genes related to thermogenesis such as Ucp1, Elovl3, Cox7a1, Cox8, and Cidea, as well as many PPAR target genes, was similar in wildtype and PPARα-/- mice. Finally, pharmacological PPARα activation had a minimal effect on expression of cold-induced genes in murine WAT. Cold-induced changes in gene expression in inguinal WAT are unaltered in mice lacking PPARα, indicating that PPARα is dispensable for cold-induced browning. Copyright © 2018 The Authors. Published by Elsevier GmbH.. All rights reserved.

Aluminium-gold reference material for the k0-standardisation of neutron activation analysis

NASA Astrophysics Data System (ADS)

Ingelbrecht, C.; Peetermans, F.; De Corte, F.; De Wispelaere, A.; Vandecasteele, C.; Courtijn, E.; D'Hondt, P.

1991-05-01

Gold is an excellent comparator material for the k0-standardisation of neutron activation analysis because of its convenient and well defined nuclear properties. The most suitable form for a reference material is a dilute aluminium-gold alloy, for which the self-shielding effect for neutrons is small. Castings of composition Al-0.1 wt.% Au were prepared by crucible-less levitation melting, which gives close control of ingot composition with minimal contamination of the melt. The alloy composition was checked using induction-coupled plasma source emission spectrometry. The homogeneity of the alloy was measured by neutron activation analysis and a relative standard deviation of the gold content of 0.30% was found (10 mg samples). Metallography revealed a homogeneous distribution of AuAl 2 particles. The alloy was certified as Reference Material CBNM-530, with certified gold mass fraction 0.100±0.002 wt.%.

Developing Coping Typologies of Minority Adolescents: A Latent Profile Analysis

PubMed Central

Aldridge, Arianna A.; Roesch, Scott C.

2008-01-01

Latent profile analysis (LPA) was used to develop a coping typology of minority adolescents (M = 15.5 yrs). A multiethnic sample (n = 354) was recruited from a program aimed at serving low-income students. LPA revealed three distinct coping profiles. The first comprised adolescents who used a number of specific coping strategies at a low level (Low Generic Copers). The second comprised adolescents who emphasized active/approach strategies (e.g., planning; Active Copers). The third comprised adolescents who emphasized avoidant/passive strategies (e.g., substance abuse; Avoidant Copers). Active Copers experienced significantly less depression and more stress-related growth than Low Generic Copers. Low Generic Copers experienced significantly less depression than Avoidant Copers but also significantly less stress-related growth than Active Copers. Discussion focuses on integrating the current typology with traditional coping taxomonies. PMID:17904631

Structure-function similarities between a plant receptor-like kinase and the human interleukin-1 receptor-associated kinase-4.

PubMed

Klaus-Heisen, Dörte; Nurisso, Alessandra; Pietraszewska-Bogiel, Anna; Mbengue, Malick; Camut, Sylvie; Timmers, Ton; Pichereaux, Carole; Rossignol, Michel; Gadella, Theodorus W J; Imberty, Anne; Lefebvre, Benoit; Cullimore, Julie V

2011-04-01

Phylogenetic analysis has previously shown that plant receptor-like kinases (RLKs) are monophyletic with respect to the kinase domain and share an evolutionary origin with the animal interleukin-1 receptor-associated kinase/Pelle-soluble kinases. The lysin motif domain-containing receptor-like kinase-3 (LYK3) of the legume Medicago truncatula shows 33% amino acid sequence identity with human IRAK-4 over the kinase domain. Using the structure of this animal kinase as a template, homology modeling revealed that the plant RLK contains structural features particular to this group of kinases, including the tyrosine gatekeeper and the N-terminal extension α-helix B. Functional analysis revealed the importance of these conserved features for kinase activity and suggests that kinase activity is essential for the biological role of LYK3 in the establishment of the root nodule nitrogen-fixing symbiosis with rhizobia bacteria. The kinase domain of LYK3 has dual serine/threonine and tyrosine specificity, and mass spectrometry analysis identified seven serine, eight threonine, and one tyrosine residue as autophosphorylation sites in vitro. Three activation loop serine/threonine residues are required for biological activity, and molecular dynamics simulations suggest that Thr-475 is the prototypical phosphorylated residue that interacts with the conserved arginine in the catalytic loop, whereas Ser-471 and Thr-472 may be secondary sites. A threonine in the juxtamembrane region and two threonines in the C-terminal lobe of the kinase domain are important for biological but not kinase activity. We present evidence that the structure-function similarities that we have identified between LYK3 and IRAK-4 may be more widely applicable to plant RLKs in general.

Experimental and DFT studies on the antioxidant activity of a C-glycoside from Rhynchosia capitata

NASA Astrophysics Data System (ADS)

Praveena, R.; Sadasivam, K.; Kumaresan, R.; Deepha, V.; Sivakumar, Raman

2013-02-01

Rhynchosia capitata (=Glycine capitata) Heyne ex roth, was found to possess polyphenolics including flavonoids, which acts as potential antioxidant. The study of ethanolic extract of roots and leaves reveals that the leaves possess high polyphenolics including flavonoids than roots. This was also confirmed by DPPH radical scavenging activity. Leaf powder of the plant was extracted with different solvents by soxhlet apparatus in the order of increasing polarity. The DPPH scavenging activity of methanol fraction was found to be high compared to the crude extract and other fractions. Nitric oxide scavenging activity was dominant in chloroform fraction compared to methanol fraction. Presence of flavonoids especially vitexin, a C-glycoside in methanol and chloroform fractions were confirmed by high pressure thin layer chromatography (HPTLC) analysis. The structural and molecular characteristics of naturally occurring flavonoid, vitexin was investigated in gas phase using density functional theory (DFT) approach with B3LYP/6-311G(d,p) level of theory. Analysis of bond dissociation enthalpy (BDE) reveals that the OH site that requires minimum energy for dissociation is 4'-OH from B-ring. To explore the radical scavenging activity of vitexin, the adiabatic ionization potential, electron affinity, hardness, softness, electronegativity and electrophilic index properties were computed and interpreted. The nonvalidity of Koopman's theorem has been verified by the computation of Eo and Ev energy magnitudes. Interestingly, from BDE calculations it was observed that BDE for 4'-OH, 5-OH and 7-OH are comparatively low for vitexin than its aglycone apigenin and this may be due to the presence of C-8 glucoside in vitexin. To substantiate this, plot of frontier molecular orbital and spin density distribution analysis for neutral and the corresponding radical species for the compound vitexin have been presented.

Pore Structure Characterization of Sodium Hydroxide Activated Slag Using Mercury Intrusion Porosimetry, Nitrogen Adsorption, and Image Analysis.

PubMed

Zuo, Yibing; Ye, Guang

2018-06-19

The pore structure of alkali-activated slag has a significant influence on its performance. However, the literature shows insufficient studies regarding the suitability of different techniques for characterizing the pore structure and the influences of Na₂O and curing age on pore structure development. In pursuit of a better understanding, the pore structure of sodium hydroxide activated slag paste was characterized by multiple techniques, e.g., mercury intrusion porosimetry (MIP), nitrogen (N₂) adsorption, and scanning electron microscopy (SEM) image analysis. The sodium hydroxide activated slag pastes were prepared with three different contents of Na₂O (Na₂O/slag = 4, 6, and 8%) and cured for different times up to 360 days. The microstructure observation reveals that outer C⁻(N⁻)A⁻S⁻H and inner C⁻(N⁻)A⁻S⁻H grow successively around the reacting slag grains, along with crystalline reaction products which are formed in the empty coarse pore space. The increase of Na₂O content and curing age lead to a finer pore structure. The MIP measurements show that the total porosity drops about 70% within the first day, and that one peak at most, corresponding to gel pores, was identified in the differential curves of all the investigated samples from 1 to 360 days. On the contrary, only one peak, corresponding to capillary pores, was identified by SEM-image analysis. The differential curves derived from N₂ adsorption generally reveal two peaks, and the trend that the pore diameters of those two peaks vary with curing age depends on the content of Na₂O. Compared to Portland cement, sodium hydroxide activated slag has a higher pore space filling capacity ( χ , V products / V slag-reacted ), while the capacity decreases with increasing Na₂O content and curing age.

Factors That Influence Park Use and Physical Activity in Predominantly Hispanic and Low-Income Neighborhoods.

PubMed

Dolash, Karry; He, Meizi; Yin, Zenong; Sosa, Erica T

2015-04-01

Park features' association with physical activity among predominantly Hispanic communities is not extensively researched. The purpose of this study was to assess factors associated with park use and physical activity among park users in predominantly Hispanic neighborhoods. Data were collected across 6 parks and included park environmental assessments to evaluate park features, physical activity observations to estimate physical activity energy expenditure as kcal/kg/ minute per person, and park user interviews to assess motivators for park use. Quantitative data analysis included independent t tests and ANOVA. Thematic analysis of park user interviews was conducted collectively and by parks. Parks that were renovated had higher physical activity energy expenditure scores (mean = .086 ± .027) than nonrenovated parks (mean = .077 ± .028; t = -3.804; P < .01). Basketball courts had a significantly higher number of vigorously active park users (mean = 1.84 ± .08) than tennis courts (mean = .15 ± .01; F = 21.9, η(2) = 6.1%, P < .01). Thematic analysis of qualitative data revealed 4 emerging themes-motivation to be physically active, using the play spaces in the park, parks as the main place for physical activity, and social support for using parks. Renovations to park amenities, such as increasing basketball courts and trail availability, could potentially increase physical activity among low-socioeconomic-status populations.

Metabolomic and elemental analysis of camel and bovine urine by GC-MS and ICP-MS.

PubMed

Ahamad, Syed Rizwan; Alhaider, Abdul Qader; Raish, Mohammad; Shakeel, Faiyaz

2017-01-01

Recent studies from the author's laboratory indicated that camel urine possesses antiplatelet activity and anti-cancer activity which is not present in bovine urine. The objective of this study is to compare the volatile and elemental components of bovine and camel urine using GC-MS and ICP-MS analysis. We are interested to know the component that performs these biological activities. The freeze dried urine was dissolved in dichloromethane and then derivatization process followed by using BSTFA for GC-MS analysis. Thirty different compounds were analyzed by the derivatization process in full scan mode. For ICP-MS analysis twenty eight important elements were analyzed in both bovine and camel urine. The results of GC-MS and ICP-MS analysis showed marked difference in the urinary metabolites. GC-MS evaluation of camel urine finds a lot of products of metabolism like benzene propanoic acid derivatives, fatty acid derivatives, amino acid derivatives, sugars, prostaglandins and canavanine. Several research reports reveal the metabolomics studies on camel urine but none of them completely reported the pharmacology related metabolomics. The present data of GC-MS suggest and support the previous studies and activities related to camel urine.

Flexible traffic control of the synfire-mode transmission by inhibitory modulation: Nonlinear noise reduction

NASA Astrophysics Data System (ADS)

Shinozaki, Takashi; Okada, Masato; Reyes, Alex D.; Câteau, Hideyuki

2010-01-01

Intermingled neural connections apparent in the brain make us wonder what controls the traffic of propagating activity in the brain to secure signal transmission without harmful crosstalk. Here, we reveal that inhibitory input but not excitatory input works as a particularly useful traffic controller because it controls the degree of synchrony of population firing of neurons as well as controlling the size of the population firing bidirectionally. Our dynamical system analysis reveals that the synchrony enhancement depends crucially on the nonlinear membrane potential dynamics and a hidden slow dynamical variable. Our electrophysiological study with rodent slice preparations show that the phenomenon happens in real neurons. Furthermore, our analysis with the Fokker-Planck equations demonstrates the phenomenon in a semianalytical manner.

Essay Contest Reveals Misconceptions of High School Students in Genetics Content

PubMed Central

Mills Shaw, Kenna R.; Van Horne, Katie; Zhang, Hubert; Boughman, Joann

2008-01-01

National educational organizations have called upon scientists to become involved in K–12 education reform. From sporadic interaction with students to more sustained partnerships with teachers, the engagement of scientists takes many forms. In this case, scientists from the American Society of Human Genetics (ASHG), the Genetics Society of America (GSA), and the National Society of Genetic Counselors (NSGC) have partnered to organize an essay contest for high school students as part of the activities surrounding National DNA Day. We describe a systematic analysis of 500 of 2443 total essays submitted in response to this contest over 2 years. Our analysis reveals the nature of student misconceptions in genetics, the possible sources of these misconceptions, and potential ways to galvanize genetics education. PMID:18245328

The effects of physical activity on impulsive choice: Influence of sensitivity to reinforcement amount and delay

PubMed Central

Strickland, Justin C.; Feinstein, Max A.; Lacy, Ryan T.; Smith, Mark A.

2016-01-01

Impulsive choice is a diagnostic feature and/or complicating factor for several psychological disorders and may be examined in the laboratory using delay-discounting procedures. Recent investigators have proposed using quantitative measures of analysis to examine the behavioral processes contributing to impulsive choice. The purpose of this study was to examine the effects of physical activity (i.e., wheel running) on impulsive choice in a single-response, discrete-trial procedure using two quantitative methods of analysis. To this end, rats were assigned to physical activity or sedentary groups and trained to respond in a delay-discounting procedure. In this procedure, one lever always produced one food pellet immediately, whereas a second lever produced three food pellets after a 0, 10, 20, 40, or 80-second delay. Estimates of sensitivity to reinforcement amount and sensitivity to reinforcement delay were determined using (1) a simple linear analysis and (2) an analysis of logarithmically transformed response ratios. Both analyses revealed that physical activity decreased sensitivity to reinforcement amount and sensitivity to reinforcement delay. These findings indicate that (1) physical activity has significant but functionally opposing effects on the behavioral processes that contribute to impulsive choice and (2) both quantitative methods of analysis are appropriate for use in single-response, discrete-trial procedures. PMID:26964905

Common and distinct neural correlates of personal and vicarious reward: A quantitative meta-analysis

PubMed Central

Morelli, Sylvia A.; Sacchet, Matthew D.; Zaki, Jamil

2015-01-01

Individuals experience reward not only when directly receiving positive outcomes (e.g., food or money), but also when observing others receive such outcomes. This latter phenomenon, known as vicarious reward, is a perennial topic of interest among psychologists and economists. More recently, neuroscientists have begun exploring the neuroanatomy underlying vicarious reward. Here we present a quantitative whole-brain meta-analysis of this emerging literature. We identified 25 functional neuroimaging studies that included contrasts between vicarious reward and a neutral control, and subjected these contrasts to an activation likelihood estimate (ALE) meta-analysis. This analysis revealed a consistent pattern of activation across studies, spanning structures typically associated with the computation of value (especially ventromedial prefrontal cortex) and mentalizing (including dorsomedial prefrontal cortex and superior temporal sulcus). We further quantitatively compared this activation pattern to activation foci from a previous meta-analysis of personal reward. Conjunction analyses yielded overlapping VMPFC activity in response to personal and vicarious reward. Contrast analyses identified preferential engagement of the nucleus accumbens in response to personal as compared to vicarious reward, and in mentalizing-related structures in response to vicarious as compared to personal reward. These data shed light on the common and unique components of the reward that individuals experience directly and through their social connections. PMID:25554428

Piloting the membranolytic activities of peptides with a self-organizing map.

PubMed

Lin, Yen-Chu; Hiss, Jan A; Schneider, Petra; Thelesklaf, Peter; Lim, Yi Fan; Pillong, Max; Koehler, Fabian M; Dittrich, Petra S; Halin, Cornelia; Wessler, Silja; Schneider, Gisbert

2014-10-13

Antimicrobial peptides (AMPs) show remarkable selectivity toward lipid membranes and possess promising antibiotic potential. Their modes of action are diverse and not fully understood, and innovative peptide design strategies are needed to generate AMPs with improved properties. We present a de novo peptide design approach that resulted in new AMPs possessing low-nanomolar membranolytic activities. Thermal analysis revealed an entropy-driven mechanism of action. The study demonstrates sustained potential of advanced computational methods for designing peptides with the desired activity. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Variant amino acid residues alter the enzyme activity of peanut type 2 Diacylglycerol Acyltransferases

USDA-ARS?s Scientific Manuscript database

Diacylglycerol acyltransferase (DGAT) catalyzes the final, rate-limiting step in triacylglycerol (TAG) biosynthesis via the acyl-CoA-dependent acylation of diacylglycerol. In this study, type-2 DGAT2 genes were cloned from eleven peanut cultivars. Sequence analysis revealed at least eight peanut D...

[New approaches to early diagnosis of chronic organophosphorus chemicals intoxication in workers at chemical weapons extermination objects].

PubMed

Babakov, V N; Goncharov, N V; Radilov, A S; Glashkina, E P; Podol'skaia, E P; Ermolaeva, E E; Shilov, V V; Prokof'eva, D S; Voĭtenko, N G; Egorov, N A

2009-01-01

Mass spectrum analysis revealed differences in general contents of low-molecular peptides spectrums in chemical weapons extermination object staffers, in comparison with the reference group. Findings are that serum paraoxonase activity in chemical weapons extermination object staffers in significantly increased.

[Health and Prevention Behaviour of Persons with and without Migration Background].

PubMed

Walter, U; Bisson, S; Gerken, U; Machleidt, W; Krauth, C

2015-09-01

Based on a sample of the Hannover registration office this project analyses the health and prevention behaviour of Russian- and Turkish-language migrants compared to natives. The project analysis revealed considerable differences, particularly concerning addiction behaviour and physical activities. © Georg Thieme Verlag KG Stuttgart · New York.

Textbook Pathos: Tracing a Through-Line of Emotion in Composition Textbooks

ERIC Educational Resources Information Center

Jensen, Tim

2016-01-01

Gretchen Flesher Moon's 2003 analysis of emotion's treatment in composition textbooks revealed that pathos "gets very short shrift" or none at all. Since then, however, conversations regarding affect and emotion have advanced in both scope and sophistication. This proliferation of scholarly activity has brought the passions of persuasion…

Polishing and parboiling effect on the nutritional and technological properties of pigmented rice

USDA-ARS?s Scientific Manuscript database

This study aims to evaluate the effects of polishing and parboiling on proximate composition, structure, phenolic compounds, antioxidant activity, cooking time and hardness of IAC-600 black rice cultivar and MPB-10 red rice lineage. Proximate analysis and light micrographs revealed higher migration ...

Changing Knowledge and the Academic Profession in Portugal

ERIC Educational Resources Information Center

Santiago, Rui; Carvalho, Teresa; Ferreira, Andreia

2015-01-01

The paper analyses the Portuguese academics' perceptions about changes in their research activities and modes of knowledge production. Quantitative data gathered from an on-line national survey have been used to develop this analysis. Results reveal that the majority of academics declared that they were not involved in knowledge and technology…

Coping Styles, Homework Compliance, and the Effectiveness of Cognitive-Behavioral Therapy.

ERIC Educational Resources Information Center

Burns, David D.; Nolen-Hoeksema, Susan

1991-01-01

Factor analysis of Self-Help Inventory from 307 outpatients receiving cognitive-behavioral therapy for affective disorders revealed 3 factors that assessed frequency of active coping strategies use when depressed, helpfulness of strategies, and willingness to learn new strategies. Frequency and Helpfulness scales were not correlated with patient…

Effects of the HN gene c-terminal extensions on the Newcastle disease virus virulence

USDA-ARS?s Scientific Manuscript database

The hemagglutinin-neuraminidase (HN) of Newcastle disease virus (NDV) is a multifunctional protein that has receptor recognition, neuraminidase and fusion promotion activities. Sequence analysis revealed that the HN gene of many extremely low virulence NDV strains encodes a larger open reading frame...

High-speed cinematography of muscle contraction.

PubMed

HAUPT, R E; WALL, D M

1962-07-13

Motion pictures of the "twitch" of an excised frog gastrocnemius muscle taken at rates of 6000 frames per second provide a means of very accurately timing the phases. The extreme "slow motion" reveals surface phenomena not observable by other techniques. Evidence of "active relaxation" is suggested by results of frame-by-frame analysis.

Young Children's Drawings in Problem Solving

ERIC Educational Resources Information Center

Bakar, Kamariah Abu; Way, Jennifer; Bobis, Janette

2016-01-01

This paper explores young children's drawings (6 years old) in early number and addition activities in Malaysia. Observation, informal interviews and analysis of drawings revealed two types of drawing, and gave insight into the transitional process required for children to utilise drawings in problem solving. We argue the importance of valuing and…

You Don't Say!: When Preservice Teachers' Public Discourse Differs from Private Opinion

ERIC Educational Resources Information Center

Fondrie, Suzanne

2009-01-01

Is what preservice teachers say about issues surrounding culture and diversity actually what they believe? Using a short critical analysis of "The Three Little Pigs," the author engages students in an anonymous writing activity that reveals dissonant opinions and leads to opportunities for discussion.

Eurasian Winter Storm Activity at the End of the Century: A CMIP5 Multi-model Ensemble Projection

NASA Astrophysics Data System (ADS)

Basu, Soumik; Zhang, Xiangdong; Wang, Zhaomin

2018-01-01

Extratropical cyclone activity over Eurasia has exhibited a weakening trend in the recent decade. Extratropical cyclones bring precipitation and hence supply fresh water for winter crops in the mid- and high-latitude regions of Eurasia. Any changes in extratropical cyclone activity over Eurasia in the future may have a critical impact on winter agriculture and the economies of affected communities. However, potential future changes in regional storm activity over Eurasia have not been studied in detail. Therefore, in this study, we investigate anticipated changes in extratropical storm activity by the end of the century through a detailed examination of the historical and future emission scenarios from six different models from CMIP5. A statistical analysis of different parameters of storm activity using a storm identification and tracking algorithm reveals a decrease in the number of storms over mid-latitude regions. However, intense storms with longer duration are projected over high latitude Eurasia. A further examination of the physical mechanism for these changes reveals that a decrease in the meridional temperature gradient and a weakening of the vertical wind shear over the mid-latitudes are responsible for these changes in storm activity.

Occidiofungin is an important component responsible for the antifungal activity of Burkholderia pyrrocinia strain Lyc2.

PubMed

Wang, X Q; Liu, A X; Guerrero, A; Liu, J; Yu, X Q; Deng, P; Ma, L; Baird, S M; Smith, L; Li, X D; Lu, S E

2016-03-01

To identify the taxonomy of tobacco rhizosphere-isolated strain Lyc2 and investigate the mechanisms of the antifungal activities, focusing on antimicrobials gene clusters identification and function analysis. Multilocus sequence typing and 16S rRNA analyses indicated that strain Lyc2 belongs to Burkholderia pyrrocinia. Bioassay results indicated strain Lyc2 showed significant antifungal activities against a broad range of plant and animal fungal pathogens and control efficacy on seedling damping off disease of cotton. A 55·2-kb gene cluster which was homologous to ocf gene clusters in Burkholderia contaminans MS14 was confirmed to be responsible for antifungal activities by random mutagenesis; HPLC was used to verify the production of antifungal compounds. Multiple antibiotic and secondary metabolized biosynthesis gene clusters predicated by antiSMASH revealed the broad spectrum of antimicrobials activities of the strain. Our results revealed the mechanisms of antifungal activities of strain Lyc2 and expand our knowledge about production of occidiofungin in the bacteria Burkholderia. Understanding the mechanisms of antifungal activities of strain Lyc2 has contributed to discovery of new antibiotics and expand our knowledge of production of occidiofungin in the bacteria Burkholderia. © 2015 The Society for Applied Microbiology.

Peatland succession induces a shift in the community composition of Sphagnum-associated active methanotrophs.

PubMed

Putkinen, Anuliina; Larmola, Tuula; Tuomivirta, Tero; Siljanen, Henri M P; Bodrossy, Levente; Tuittila, Eeva-Stiina; Fritze, Hannu

2014-06-01

Sphagnum-associated methanotrophs (SAM) are an important sink for the methane (CH4) formed in boreal peatlands. We aimed to reveal how peatland succession, which entails a directional change in several environmental variables, affects SAM and their activity. Based on the pmoA microarray results, SAM community structure changes when a peatland develops from a minerotrophic fen to an ombrotrophic bog. Methanotroph subtypes Ia, Ib, and II showed slightly contrasting patterns during succession, suggesting differences in their ecological niche adaptation. Although the direct DNA-based analysis revealed a high diversity of type Ib and II methanotrophs throughout the studied peatland chronosequence, stable isotope probing (SIP) of the pmoA gene indicated they were active mainly during the later stages of succession. In contrast, type Ia methanotrophs showed active CH4 consumption in all analyzed samples. SIP-derived (13)C-labeled 16S rRNA gene clone libraries revealed a high diversity of SAM in every succession stage including some putative Methylocella/Methyloferula methanotrophs that are not detectable with the pmoA-based approach. In addition, a high diversity of 16S rRNA gene sequences likely representing cross-labeled nonmethanotrophs was discovered, including a significant proportion of Verrucomicrobia-related sequences. These results help to predict the effects of changing environmental conditions on SAM communities and activity. © 2014 Federation of European Microbiological Societies. Published by John Wiley & Sons Ltd. All rights reserved.

Identification and structural characterization of a new pro-apoptotic cyclic octapeptide cyclosaplin from somatic seedlings of Santalum album L.

PubMed

Mishra, Abheepsa; Gauri, Samiran S; Mukhopadhyay, Sourav K; Chatterjee, Soumya; Das, Shibendu S; Mandal, Santi M; Dey, Satyahari

2014-04-01

Small cyclic peptides exhibiting potent biological activity have great potential for anticancer therapy. An antiproliferative cyclic octapeptide, cyclosaplin was purified from somatic seedlings of Santalum album L. (sandalwood) using gel filtration and RP-HPLC separation process. The molecular mass of purified peptide was found to be 858 Da and the sequence was determined by MALDI-ToF-PSD-MS as 'RLGDGCTR' (cyclic). The cytotoxic activity of the peptide was tested against human breast cancer (MDA-MB-231) cell line in a dose and time-dependent manner. The purified peptide exhibited significant antiproliferative activity with an IC50 2.06 μg/mL. In a mechanistic approach, apoptosis was observed in differential microscopic studies for peptide treated MDA-MB-231 cells, which was further confirmed by mitochondrial membrane potential, DNA fragmentation assay, cell cycle analysis and caspase 3 activities. The modeling and docking experiments revealed strong affinity (kcal/mol) of peptide toward EGFR and procaspase 3. The co-localization studies revealed that the peptide sensitizes MDA-MB-231 cells by possibly binding to EGFR and induces apoptosis. This unique cyclic octapeptide revealed to be a favorable candidate for development of anticancer agents. Copyright © 2014 Elsevier Inc. All rights reserved.

How acute total sleep loss affects the attending brain: a meta-analysis of neuroimaging studies.

PubMed

Ma, Ning; Dinges, David F; Basner, Mathias; Rao, Hengyi

2015-02-01

Attention is a cognitive domain that can be severely affected by sleep deprivation. Previous neuroimaging studies have used different attention paradigms and reported both increased and reduced brain activation after sleep deprivation. However, due to large variability in sleep deprivation protocols, task paradigms, experimental designs, characteristics of subject populations, and imaging techniques, there is no consensus regarding the effects of sleep loss on the attending brain. The aim of this meta-analysis was to identify brain activations that are commonly altered by acute total sleep deprivation across different attention tasks. Coordinate-based meta-analysis of neuroimaging studies of performance on attention tasks during experimental sleep deprivation. The current version of the activation likelihood estimation (ALE) approach was used for meta-analysis. The authors searched published articles and identified 11 sleep deprivation neuroimaging studies using different attention tasks with a total of 185 participants, equaling 81 foci for ALE analysis. The meta-analysis revealed significantly reduced brain activation in multiple regions following sleep deprivation compared to rested wakefulness, including bilateral intraparietal sulcus, bilateral insula, right prefrontal cortex, medial frontal cortex, and right parahippocampal gyrus. Increased activation was found only in bilateral thalamus after sleep deprivation compared to rested wakefulness. Acute total sleep deprivation decreases brain activation in the fronto-parietal attention network (prefrontal cortex and intraparietal sulcus) and in the salience network (insula and medial frontal cortex). Increased thalamic activation after sleep deprivation may reflect a complex interaction between the de-arousing effects of sleep loss and the arousing effects of task performance on thalamic activity. © 2015 Associated Professional Sleep Societies, LLC.

Identification of IL-1β and LPS as optimal activators of monolayer and alginate-encapsulated mesenchymal stromal cell immunomodulation using design of experiments and statistical methods.

PubMed

Gray, Andrea; Maguire, Timothy; Schloss, Rene; Yarmush, Martin L

2015-01-01

Induction of therapeutic mesenchymal stromal cell (MSC) function is dependent upon activating factors present in diseased or injured tissue microenvironments. These functions include modulation of macrophage phenotype via secreted molecules including prostaglandin E2 (PGE2). Many approaches aim to optimize MSC-based therapies, including preconditioning using soluble factors and cell immobilization in biomaterials. However, optimization of MSC function is usually inefficient as only a few factors are manipulated in parallel. We utilized fractional factorial design of experiments to screen a panel of 6 molecules (lipopolysaccharide [LPS], polyinosinic-polycytidylic acid [poly(I:C)], interleukin [IL]-6, IL-1β, interferon [IFN]-β, and IFN-γ), individually and in combinations, for the upregulation of MSC PGE2 secretion and attenuation of macrophage secretion of tumor necrosis factor (TNF)-α, a pro-inflammatory molecule, by activated-MSC conditioned medium (CM). We used multivariable linear regression (MLR) and analysis of covariance to determine differences in functions of optimal factors on monolayer MSCs and alginate-encapsulated MSCs (eMSCs). The screen revealed that LPS and IL-1β potently activated monolayer MSCs to enhance PGE2 production and attenuate macrophage TNF-α. Activation by LPS and IL-1β together synergistically increased MSC PGE2, but did not synergistically reduce macrophage TNF-α. MLR and covariate analysis revealed that macrophage TNF-α was strongly dependent on the MSC activation factor, PGE2 level, and macrophage donor but not MSC culture format (monolayer versus encapsulated). The results demonstrate the feasibility and utility of using statistical approaches for higher throughput cell analysis. This approach can be extended to develop activation schemes to maximize MSC and MSC-biomaterial functions prior to transplantation to improve MSC therapies. © 2015 American Institute of Chemical Engineers.

My Body Looks Like That Girl’s: Body Mass Index Modulates Brain Activity during Body Image Self-Reflection among Young Women

PubMed Central

Wen, Xin; She, Ying; Vinke, Petra Corianne; Chen, Hong

2016-01-01

Body image distress or body dissatisfaction is one of the most common consequences of obesity and overweight. We investigated the neural bases of body image processing in overweight and average weight young women to understand whether brain regions that were previously found to be involved in processing self-reflective, perspective and affective components of body image would show different activation between two groups. Thirteen overweight (O-W group, age = 20.31±1.70 years) and thirteen average weight (A-W group, age = 20.15±1.62 years) young women underwent functional magnetic resonance imaging while performing a body image self-reflection task. Among both groups, whole-brain analysis revealed activations of a brain network related to perceptive and affective components of body image processing. ROI analysis showed a main effect of group in ACC as well as a group by condition interaction within bilateral EBA, bilateral FBA, right IPL, bilateral DLPFC, left amygdala and left MPFC. For the A-W group, simple effect analysis revealed stronger activations in Thin-Control compared to Fat-Control condition within regions related to perceptive (including bilateral EBA, bilateral FBA, right IPL) and affective components of body image processing (including bilateral DLPFC, left amygdala), as well as self-reference (left MPFC). The O-W group only showed stronger activations in Fat-Control than in Thin-Control condition within regions related to the perceptive component of body image processing (including left EBA and left FBA). Path analysis showed that in the Fat-Thin contrast, body dissatisfaction completely mediated the group difference in brain response in left amygdala across the whole sample. Our data are the first to demonstrate differences in brain response to body pictures between average weight and overweight young females involved in a body image self-reflection task. These results provide insights for understanding the vulnerability to body image distress among overweight or obese young females. PMID:27764116

My Body Looks Like That Girl's: Body Mass Index Modulates Brain Activity during Body Image Self-Reflection among Young Women.

PubMed

Gao, Xiao; Deng, Xiao; Wen, Xin; She, Ying; Vinke, Petra Corianne; Chen, Hong

2016-01-01

Body image distress or body dissatisfaction is one of the most common consequences of obesity and overweight. We investigated the neural bases of body image processing in overweight and average weight young women to understand whether brain regions that were previously found to be involved in processing self-reflective, perspective and affective components of body image would show different activation between two groups. Thirteen overweight (O-W group, age = 20.31±1.70 years) and thirteen average weight (A-W group, age = 20.15±1.62 years) young women underwent functional magnetic resonance imaging while performing a body image self-reflection task. Among both groups, whole-brain analysis revealed activations of a brain network related to perceptive and affective components of body image processing. ROI analysis showed a main effect of group in ACC as well as a group by condition interaction within bilateral EBA, bilateral FBA, right IPL, bilateral DLPFC, left amygdala and left MPFC. For the A-W group, simple effect analysis revealed stronger activations in Thin-Control compared to Fat-Control condition within regions related to perceptive (including bilateral EBA, bilateral FBA, right IPL) and affective components of body image processing (including bilateral DLPFC, left amygdala), as well as self-reference (left MPFC). The O-W group only showed stronger activations in Fat-Control than in Thin-Control condition within regions related to the perceptive component of body image processing (including left EBA and left FBA). Path analysis showed that in the Fat-Thin contrast, body dissatisfaction completely mediated the group difference in brain response in left amygdala across the whole sample. Our data are the first to demonstrate differences in brain response to body pictures between average weight and overweight young females involved in a body image self-reflection task. These results provide insights for understanding the vulnerability to body image distress among overweight or obese young females.

GM2 Activator Deficiency Caused by a Homozygous Exon 2 Deletion in GM2A.

PubMed

Hall, Patricia L; Laine, Regina; Alexander, John J; Ankala, Arunkanth; Teot, Lisa A; Lidov, Hart G W; Anselm, Irina

2018-01-01

GM2 activator (GM2A) deficiency (OMIM 613109) is a rare lysosomal storage disorder, with onset typically in infancy or early childhood. Clinically, it is almost indistinguishable from Tay-Sachs disease (OMIM 272800) or Sandhoff disease (OMIM 268800); however, traditionally available biochemical screening tests will most likely reveal normal results. We report a 2-year-old male with initially normal development until the age of 9 months, when he presented with developmental delay and regression. Workup at that time was unrevealing; at 15 months, he had abnormal brain MRI findings and a cherry red spot on ophthalmological examination. Family history and all laboratory studies were uninformative. The combination of a cherry red spot and developmental regression was strongly suggestive of a lysosomal storage disorder. Sequence analysis of GM2A did not reveal any pathogenic variants; however, exon 2 of GM2A could not be amplified by PCR, raising suspicion for a large, homozygous deletion. Subsequent copy number analysis confirmed a homozygous deletion of exon 2 in GM2A. This is the first reported case of GM2A deficiency being caused by a whole exon deletion. We describe previously unreported electron microscopy findings in this disease, thus expanding the clinical and variant spectrum for GM2 activator deficiency. These findings demonstrate the increased degree of suspicion required for diagnosis of this rare disorder. Brief Summary: This case of GM2 activator deficiency was caused by a homozygous deletion in GM2A, demonstrating the need to include exon level copy number analysis in any workup to fully exclude this disorder.

[Effect of low-intensity 900 MHz frequency electromagnetic radiation on rat liver and blood serum enzyme activities].

PubMed

Nersesova, L S; Petrosian, M S; Gazariants, M G; Mkrtchian, Z S; Meliksetian, G O; Pogosian, L G; Akopian, Zh I

2014-01-01

The comparative analysis of the rat liver and blood serum creatine kinase, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase and purine nucleoside phosphorylase post-radiation activity levels after a total two-hour long single and fractional exposure of the animals to low-intensity 900 MHz frequency electromagnetic field showed that the most sensitive enzymes to the both schedules of radiation are the liver creatine kinase, as well as the blood serum creatine kinase and alkaline phosphatase. According to the comparative analysis of the dynamics of changes in the activity level of the liver and blood serum creatine kinase, alanine aminotransferase, aspartate aminotransferase and purine nucleoside phosphorylase, both single and fractional radiation schedules do not affect the permeability of a hepatocyte cell membrane, but rather cause changes in their energetic metabolism. The correlation analysis of the post-radiation activity level changes of the investigated enzymes did not reveal a clear relationship between them. The dynamics of post-radiation changes in the activity of investigated enzyme levels following a single and short-term fractional schedules of radiation did not differ essentially.

Structure of granzyme C reveals an unusual mechanism of protease autoinhibition

PubMed Central

Kaiserman, Dion; Buckle, Ashley M.; Van Damme, Petra; Irving, James A.; Law, Ruby H. P.; Matthews, Antony Y.; Bashtannyk-Puhalovich, Tanya; Langendorf, Chris; Thompson, Philip; Vandekerckhove, Joël; Gevaert, Kris; Whisstock, James C.; Bird, Phillip I.

2009-01-01

Proteases act in important homeostatic pathways and are tightly regulated. Here, we report an unusual structural mechanism of regulation observed by the 2.5-Å X-ray crystal structure of the serine protease, granzyme C. Although the active-site triad residues adopt canonical conformations, the oxyanion hole is improperly formed, and access to the primary specificity (S1) pocket is blocked through a reversible rearrangement involving Phe-191. Specifically, a register shift in the 190-strand preceding the active-site serine leads to Phe-191 filling the S1 pocket. Mutation of a unique Glu–Glu motif at positions 192–193 unlocks the enzyme, which displays chymase activity, and proteomic analysis confirms that activity of the wild-type protease can be released through interactions with an appropriate substrate. The 2.5-Å structure of the unlocked enzyme reveals unprecedented flexibility in the 190-strand preceding the active-site serine that results in Phe-191 vacating the S1 pocket. Overall, these observations describe a broadly applicable mechanism of protease regulation that cannot be predicted by template-based modeling or bioinformatic approaches alone. PMID:19299505

Earthworm tolerance to residual agricultural pesticide contamination: field and experimental assessment of detoxification capabilities.

PubMed

Givaudan, Nicolas; Binet, Françoise; Le Bot, Barbara; Wiegand, Claudia

2014-09-01

This study investigates if acclimatization to residual pesticide contamination in agricultural soils is reflected in detoxification, antioxidant enzyme activities and energy budget of earthworms. Five fields within a joint agricultural area exhibited different chemical and farming histories from conventional cultivation to organic pasture. Soil multiresidual pesticide analysis revealed up to 9 molecules including atrazine up to 2.4 ng g(-1) dry soil. Exposure history of endogeic Aporrectodea caliginosa and Allolobophora chlorotica modified their responses to pesticides. In the field, activities of soluble glutathione-S-transferases (sGST) and catalase increased with soil pesticide contamination in A. caliginosa. Pesticide stress was reflected in depletion of energy reserves in A. chlorotica. Acute exposure of pre-adapted and naïve A. caliginosa to pesticides (fungicide Opus(®), 0.1 μg active ingredient epoxiconazole g(-1) dry soil, RoundUp Flash(®), 2.5 μg active ingredient glyphosate g(-1) dry soil, and their mixture), revealed that environmental pre-exposure accelerated activation of the detoxification enzyme sGST towards epoxiconazole. Copyright © 2014 Elsevier Ltd. All rights reserved.

Attempting to be active: Self-efficacy and barrier limitation differentiate activity levels of working mothers.

PubMed

Gierc, Madelaine; Locke, Sean; Jung, Mary; Brawley, Lawrence

2016-07-01

Working mothers are less physically active than working women without children and mothers who do not work. The purpose of this study was to examine concurrent self-regulatory efficacy and barriers to physical activity in a sample of working mothers. Women completed a mixed-methods survey which included measures of physical activity, concurrent self-regulatory efficacy, and barriers. Sufficiently active women experienced significantly greater concurrent self-regulatory efficacy and significantly less barrier limitation and frequency. No significant group differences were found for age, domestic duties performed, and children's extracurricular activities. Thematic analysis of barriers revealed six themes of common and unique factors, including limited time and family activities. © The Author(s) 2014.

Comparative genomic analysis of SET domain family reveals the origin, expansion, and putative function of the arthropod-specific SmydA genes as histone modifiers in insects.

PubMed

Jiang, Feng; Liu, Qing; Wang, Yanli; Zhang, Jie; Wang, Huimin; Song, Tianqi; Yang, Meiling; Wang, Xianhui; Kang, Le

2017-06-01

The SET domain is an evolutionarily conserved motif present in histone lysine methyltransferases, which are important in the regulation of chromatin and gene expression in animals. In this study, we searched for SET domain-containing genes (SET genes) in all of the 147 arthropod genomes sequenced at the time of carrying out this experiment to understand the evolutionary history by which SET domains have evolved in insects. Phylogenetic and ancestral state reconstruction analysis revealed an arthropod-specific SET gene family, named SmydA, that is ancestral to arthropod animals and specifically diversified during insect evolution. Considering that pseudogenization is the most probable fate of the new emerging gene copies, we provided experimental and evolutionary evidence to demonstrate their essential functions. Fluorescence in situ hybridization analysis and in vitro methyltransferase activity assays showed that the SmydA-2 gene was transcriptionally active and retained the original histone methylation activity. Expression knockdown by RNA interference significantly increased mortality, implying that the SmydA genes may be essential for insect survival. We further showed predominantly strong purifying selection on the SmydA gene family and a potential association between the regulation of gene expression and insect phenotypic plasticity by transcriptome analysis. Overall, these data suggest that the SmydA gene family retains essential functions that may possibly define novel regulatory pathways in insects. This work provides insights into the roles of lineage-specific domain duplication in insect evolution. © The Authors 2017. Published by Oxford University Press.

An effectiveness and cost-benefit analysis of a hospital-based discharge transition program for elderly Medicare recipients.

PubMed

Saleh, Shadi S; Freire, Chris; Morris-Dickinson, Gwendolyn; Shannon, Trip

2012-06-01

To investigate the business case of postdischarge care transition (PDCT) among Medicare beneficiaries by conducting a cost-benefit analysis. Randomized controlled trial. A general hospital in upstate New York State. Elderly Medicare beneficiaries being treated from October 2008 through December 2009 were randomly selected to receive services as part of a comprehensive PDCT program (intervention--173 patients) or regular discharge process (control--160 patients) and followed for 12 months. The intervention comprised five activities: development of a patient-centered health record, a structured discharge preparation checklist of critical activities, delivery of patient self-activation and management sessions, follow-up appointments, and coordination of data flow. Cost-benefit ratio of the PDCT program; self-management skills and abilities. The 1-year readmission analysis revealed that control participants were more likely to be readmitted than intervention participants (58.2% vs 48.2%; P = .08); with most of that difference observed in the 91 to 365 days after discharge. Findings from the cost-benefit analysis revealed a cost-benefit ratio of 1.09, which indicates that, for every $1 spent on the program, a saving of $1.09 was realized. In addition, participating in a care transition program significantly enhanced self-management skills and abilities. Postdischarge care transition programs have a dual benefit of enhancing elderly adults' self-management skills and abilities and producing cost savings. This study builds a case for the inclusion of PDCT programs as a reimbursable service in benefit packages. © 2012, Copyright the Authors Journal compilation © 2012, The American Geriatrics Society.

Comparative genomic analysis of SET domain family reveals the origin, expansion, and putative function of the arthropod-specific SmydA genes as histone modifiers in insects

PubMed Central

Jiang, Feng; Liu, Qing; Wang, Yanli; Zhang, Jie; Wang, Huimin; Song, Tianqi; Yang, Meiling

2017-01-01

Abstract The SET domain is an evolutionarily conserved motif present in histone lysine methyltransferases, which are important in the regulation of chromatin and gene expression in animals. In this study, we searched for SET domain–containing genes (SET genes) in all of the 147 arthropod genomes sequenced at the time of carrying out this experiment to understand the evolutionary history by which SET domains have evolved in insects. Phylogenetic and ancestral state reconstruction analysis revealed an arthropod-specific SET gene family, named SmydA, that is ancestral to arthropod animals and specifically diversified during insect evolution. Considering that pseudogenization is the most probable fate of the new emerging gene copies, we provided experimental and evolutionary evidence to demonstrate their essential functions. Fluorescence in situ hybridization analysis and in vitro methyltransferase activity assays showed that the SmydA-2 gene was transcriptionally active and retained the original histone methylation activity. Expression knockdown by RNA interference significantly increased mortality, implying that the SmydA genes may be essential for insect survival. We further showed predominantly strong purifying selection on the SmydA gene family and a potential association between the regulation of gene expression and insect phenotypic plasticity by transcriptome analysis. Overall, these data suggest that the SmydA gene family retains essential functions that may possibly define novel regulatory pathways in insects. This work provides insights into the roles of lineage-specific domain duplication in insect evolution. PMID:28444351

How Acute Total Sleep Loss Affects the Attending Brain: A Meta-Analysis of Neuroimaging Studies

PubMed Central

Ma, Ning; Dinges, David F.; Basner, Mathias; Rao, Hengyi

2015-01-01

Study Objectives: Attention is a cognitive domain that can be severely affected by sleep deprivation. Previous neuroimaging studies have used different attention paradigms and reported both increased and reduced brain activation after sleep deprivation. However, due to large variability in sleep deprivation protocols, task paradigms, experimental designs, characteristics of subject populations, and imaging techniques, there is no consensus regarding the effects of sleep loss on the attending brain. The aim of this meta-analysis was to identify brain activations that are commonly altered by acute total sleep deprivation across different attention tasks. Design: Coordinate-based meta-analysis of neuroimaging studies of performance on attention tasks during experimental sleep deprivation. Methods: The current version of the activation likelihood estimation (ALE) approach was used for meta-analysis. The authors searched published articles and identified 11 sleep deprivation neuroimaging studies using different attention tasks with a total of 185 participants, equaling 81 foci for ALE analysis. Results: The meta-analysis revealed significantly reduced brain activation in multiple regions following sleep deprivation compared to rested wakefulness, including bilateral intraparietal sulcus, bilateral insula, right prefrontal cortex, medial frontal cortex, and right parahippocampal gyrus. Increased activation was found only in bilateral thalamus after sleep deprivation compared to rested wakefulness. Conclusion: Acute total sleep deprivation decreases brain activation in the fronto-parietal attention network (prefrontal cortex and intraparietal sulcus) and in the salience network (insula and medial frontal cortex). Increased thalamic activation after sleep deprivation may reflect a complex interaction between the de-arousing effects of sleep loss and the arousing effects of task performance on thalamic activity. Citation: Ma N, Dinges DF, Basner M, Rao H. How acute total sleep loss affects the attending brain: a meta-analysis of neuroimaging studies. SLEEP 2015;38(2):233–240. PMID:25409102

Structural and Functional Analysis of a Lytic Polysaccharide Monooxygenase Important for Efficient Utilization of Chitin in Cellvibrio japonicus*

PubMed Central

Forsberg, Zarah; Nelson, Cassandra E.; Dalhus, Bjørn; Mekasha, Sophanit; Loose, Jennifer S. M.; Crouch, Lucy I.; Røhr, Åsmund K.; Gardner, Jeffrey G.; Eijsink, Vincent G. H.; Vaaje-Kolstad, Gustav

2016-01-01

Cellvibrio japonicus is a Gram-negative soil bacterium that is primarily known for its ability to degrade plant cell wall polysaccharides through utilization of an extensive repertoire of carbohydrate-active enzymes. Several putative chitin-degrading enzymes are also found among these carbohydrate-active enzymes, such as chitinases, chitobiases, and lytic polysaccharide monooxygenases (LPMOs). In this study, we have characterized the chitin-active LPMO, CjLPMO10A, a tri-modular enzyme containing a catalytic family AA10 LPMO module, a family 5 chitin-binding module, and a C-terminal unclassified module of unknown function. Characterization of the latter module revealed tight and specific binding to chitin, thereby unraveling a new family of chitin-binding modules (classified as CBM73). X-ray crystallographic elucidation of the CjLPMO10A catalytic module revealed that the active site of the enzyme combines structural features previously only observed in either cellulose or chitin-active LPMO10s. Analysis of the copper-binding site by EPR showed a signal signature more similar to those observed for cellulose-cleaving LPMOs. The full-length LPMO shows no activity toward cellulose but is able to bind and cleave both α- and β-chitin. Removal of the chitin-binding modules reduced LPMO activity toward α-chitin compared with the full-length enzyme. Interestingly, the full-length enzyme and the individual catalytic LPMO module boosted the activity of an endochitinase equally well, also yielding similar amounts of oxidized products. Finally, gene deletion studies show that CjLPMO10A is needed by C. japonicus to obtain efficient growth on both purified chitin and crab shell particles. PMID:26858252

Structural and Functional Analysis of a Lytic Polysaccharide Monooxygenase Important for Efficient Utilization of Chitin in Cellvibrio japonicus.

PubMed

Forsberg, Zarah; Nelson, Cassandra E; Dalhus, Bjørn; Mekasha, Sophanit; Loose, Jennifer S M; Crouch, Lucy I; Røhr, Åsmund K; Gardner, Jeffrey G; Eijsink, Vincent G H; Vaaje-Kolstad, Gustav

2016-04-01

Cellvibrio japonicusis a Gram-negative soil bacterium that is primarily known for its ability to degrade plant cell wall polysaccharides through utilization of an extensive repertoire of carbohydrate-active enzymes. Several putative chitin-degrading enzymes are also found among these carbohydrate-active enzymes, such as chitinases, chitobiases, and lytic polysaccharide monooxygenases (LPMOs). In this study, we have characterized the chitin-active LPMO,CjLPMO10A, a tri-modular enzyme containing a catalytic family AA10 LPMO module, a family 5 chitin-binding module, and a C-terminal unclassified module of unknown function. Characterization of the latter module revealed tight and specific binding to chitin, thereby unraveling a new family of chitin-binding modules (classified as CBM73). X-ray crystallographic elucidation of theCjLPMO10A catalytic module revealed that the active site of the enzyme combines structural features previously only observed in either cellulose or chitin-active LPMO10s. Analysis of the copper-binding site by EPR showed a signal signature more similar to those observed for cellulose-cleaving LPMOs. The full-length LPMO shows no activity toward cellulose but is able to bind and cleave both α- and β-chitin. Removal of the chitin-binding modules reduced LPMO activity toward α-chitin compared with the full-length enzyme. Interestingly, the full-length enzyme and the individual catalytic LPMO module boosted the activity of an endochitinase equally well, also yielding similar amounts of oxidized products. Finally, gene deletion studies show thatCjLPMO10A is needed byC. japonicusto obtain efficient growth on both purified chitin and crab shell particles. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Exogenous vs. endogenous attention: Shifting the balance of fronto-parietal activity.

PubMed

Meyer, Kristin N; Du, Feng; Parks, Emily; Hopfinger, Joseph B

2018-03-01

Despite behavioral and electrophysiological evidence for dissociations between endogenous (voluntary) and exogenous (reflexive) attention, fMRI results have yet to consistently and clearly differentiate neural activation patterns between these two types of attention. This study specifically aimed to determine whether activity in the dorsal fronto-parietal network differed between endogenous and exogenous conditions. Participants performed a visual discrimination task in endogenous and exogenous attention conditions while undergoing fMRI scanning. Analyses revealed robust and bilateral activation throughout the dorsal fronto-parietal network for each condition, in line with many previous results. In order to investigate possible differences in the balance of neural activity within this network with greater sensitivity, a priori regions of interest (ROIs) were selected for analysis, centered on the frontal eye fields (FEF) and intraparietal sulcus (IPS) regions identified in previous studies. The results revealed a significant interaction between region, condition, and hemisphere. Specifically, in the left hemisphere, frontal areas were more active than parietal areas, but only during endogenous attention. Activity in the right hemisphere, in contrast, remained relatively consistent for these regions across conditions. Analysis of this activity over time indicates that this left-hemispheric regional imbalance is present within the FEF early, at 3-6.5 s post-stimulus presentation, whereas a regional imbalance in the exogenous condition is not evident until 6.5-8 s post-stimulus presentation. Overall, our results provide new evidence that although the dorsal fronto-parietal network is indeed associated with both types of attentional orienting, regions of the network are differentially engaged over time and across hemispheres depending on the type of attention. Copyright © 2018 Elsevier Ltd. All rights reserved.

Characterization of inhibitory effects of the potential therapeutic inhibitors, benzoic acid and pyridine derivatives, on the monophenolase and diphenolase activities of tyrosinase.

PubMed

Gheibi, Nematollah; Taherkhani, Negar; Ahmadi, Abolfazl; Haghbeen, Kamahldin; Ilghari, Dariush

2015-02-01

Involvement of tyrosinase in the synthesis of melanin and cell signaling pathway has made it an attractive target in the search for therapeutic inhibitors for treatment of different skin hyperpigmentation disorders and melanoma cancers. In the present study, we conducted a comprehensive kinetic analysis to understand the mechanisms of inhibition imposed by 2-amino benzoic acid, 4-amino benzoic acid, nicotinic acid, and picolinic acid on the monophenolase and diphenolase activities of the mushroom tyrosinase, and then MTT assay was exploited to evaluate their toxicity on the melanoma cells. Kinetic analysis revealed that nicotinic acid and picolinic acid competitively restricted the monophenolase activity with inhibition constants (Ki) of 1.21 mM and 1.97 mM and the diphenolase activity with Kis of 2.4 mM and 2.93 mM, respectively. 2-aminobenzoic acid and 4-aminobenzoic acid inhibited the monophenolase activity in a non-competitive fashion with Kis of 5.15 µM and 3.8 µM and the diphenolase activity with Kis of 4.72 µM and 20 µM, respectively. Our cell-based data revealed that only the pyridine derivatives imposed cytotoxicity in melanoma cells. Importantly, the concentrations of the inhibitors leading to 50% decrease in the cell density (IC50) were comparable to those causing 50% drop in the enzyme activity, implying that the observed cytotoxicity is highly likely due to the tyrosinase inhibition. Moreover, our cell-based data exhibited that the pyridine derivatives acted as anti-proliferative agents, perhaps inducing cytotoxicity in the melanoma cells through inhibition of the tyrosinase activities.

Characterization of inhibitory effects of the potential therapeutic inhibitors, benzoic acid and pyridine derivatives, on the monophenolase and diphenolase activities of tyrosinase

PubMed Central

Gheibi, Nematollah; Taherkhani, Negar; Ahmadi, Abolfazl; Haghbeen, Kamahldin; Ilghari, Dariush

2015-01-01

Objective(s): Involvement of tyrosinase in the synthesis of melanin and cell signaling pathway has made it an attractive target in the search for therapeutic inhibitors for treatment of different skin hyperpigmentation disorders and melanoma cancers. Materials and Methods: In the present study, we conducted a comprehensive kinetic analysis to understand the mechanisms of inhibition imposed by 2-amino benzoic acid, 4-amino benzoic acid, nicotinic acid, and picolinic acid on the monophenolase and diphenolase activities of the mushroom tyrosinase, and then MTT assay was exploited to evaluate their toxicity on the melanoma cells. Results: Kinetic analysis revealed that nicotinic acid and picolinic acid competitively restricted the monophenolase activity with inhibition constants (Ki) of 1.21 mM and 1.97 mM and the diphenolase activity with Kis of 2.4 mM and 2.93 mM, respectively. 2-aminobenzoic acid and 4-aminobenzoic acid inhibited the monophenolase activity in a non-competitive fashion with Kis of 5.15 µM and 3.8 µM and the diphenolase activity with Kis of 4.72 µM and 20 µM, respectively. Conclusion: Our cell-based data revealed that only the pyridine derivatives imposed cytotoxicity in melanoma cells. Importantly, the concentrations of the inhibitors leading to 50% decrease in the cell density (IC50) were comparable to those causing 50% drop in the enzyme activity, implying that the observed cytotoxicity is highly likely due to the tyrosinase inhibition. Moreover, our cell-based data exhibited that the pyridine derivatives acted as anti-proliferative agents, perhaps inducing cytotoxicity in the melanoma cells through inhibition of the tyrosinase activities. PMID:25810885

Bayesian network analysis revealed the connectivity difference of the default mode network from the resting-state to task-state

PubMed Central

Wu, Xia; Yu, Xinyu; Yao, Li; Li, Rui

2014-01-01

Functional magnetic resonance imaging (fMRI) studies have converged to reveal the default mode network (DMN), a constellation of regions that display co-activation during resting-state but co-deactivation during attention-demanding tasks in the brain. Here, we employed a Bayesian network (BN) analysis method to construct a directed effective connectivity model of the DMN and compared the organizational architecture and interregional directed connections under both resting-state and task-state. The analysis results indicated that the DMN was consistently organized into two closely interacting subsystems in both resting-state and task-state. The directed connections between DMN regions, however, changed significantly from the resting-state to task-state condition. The results suggest that the DMN intrinsically maintains a relatively stable structure whether at rest or performing tasks but has different information processing mechanisms under varied states. PMID:25309414

Paradoxes of the comparative analysis of ground-based and satellite geodetic measurements in recent geodynamics

NASA Astrophysics Data System (ADS)

Kuzmin, Yu. O.

2017-11-01

The comparative analysis of the Earth's surface deformations measured by ground-based and satellite geodetic methods on the regional and zonal measurement scales is carried out. The displacement velocities and strain rates are compared in the active regions such as Turkmenian-Iranian zone of interaction of the Arabian and Eurasian lithospheric plates and the Kamchatka segment of the subduction of the Pacific Plate beneath the Okotsk Plate. The comparison yields a paradoxical result. With the qualitatively identical kinematics of the motion, the quantitative characteristics of the displacement velocities and rates of strain revealed by the observations using the global navigational satellite system (GNSS) are by 1-2 orders of magnitude higher than those estimated by the more accurate methods of ground-based geodesy. For resolving the revealed paradoxes, it is required to set up special studies on the joint analysis of ground-based and satellite geodetic data from the combined observation sites.

Kocuria marina BS-15 a biosurfactant producing halophilic bacteria isolated from solar salt works in India

PubMed Central

Sarafin, Yesurethinam; Donio, Mariathasan Birdilla Selva; Velmurugan, Subramanian; Michaelbabu, Mariavincent; Citarasu, Thavasimuthu

2014-01-01

Biosurfactant screening was made among the eight halophilic bacterial genera isolated from Kovalam solar salt works in Kanyakumari of India. After initial screening, Kocuria sp. (Km), Kurthia sp. (Ku) and Halococcus sp. (Hc) were found to have positive biosurfactant activity. Biosurfactant derived from Kocuria sp. emulsified more than 50% of the crude oil, coconut oil, sunflower oil, olive oil and kerosene when compared to the other strains. Further, Kocuria marina BS-15 derived biosurfactant was purified and characterized by TLC, FTIR and GC–MS analysis. The TLC analysis revealed that, the purified biosurfactants belong to the lipopeptide group. The IR spectrum results revealed that functional groups are R2C 000000000000 000000000000 000000000000 111111111111 000000000000 111111111111 000000000000 000000000000 000000000000 NN, alkenes and N–H. The GC–MS analysis confirmed the compound as Nonanoic acid and Cyclopropane with the retention time of 12.78 and 24.65, respectively. PMID:25473358

Using alcohol to sell cigarettes to young adults: a content analysis of cigarette advertisements.

PubMed

Belstock, Sarah A; Connolly, Gregory N; Carpenter, Carrie M; Tucker, Lindsey

2008-01-01

Advertising influences the health-related behaviors of college-aged individuals. Cigarette manufacturers aggressively market to young adults and may exploit their affinity for alcohol when creating advertisements designed to increase cigarettes' appeal. Internal tobacco industry documents reveal that cigarette manufacturers understood the popularity of alcohol among young adults and sought to produce pertinent marketing strategies. The authors conducted a content analysis of cigarette and alcohol advertisements in young adult-oriented magazines to investigate portrayed associations between cigarettes and alcohol. The content analysis revealed that 32 of 114 cigarette advertisements referenced alcohol and that those advertisements were more likely than others to portray active smoking. Conversely, 0 of 317 alcohol advertisements referenced cigarettes, and alcohol advertisements were only slightly more likely than cigarette advertisements to feature alcohol-related settings. Such advertising may detrimentally affect smoking patterns of college students. An understanding of these strategies can benefit on-campus tobacco control efforts.

Decision Support System Requirements Definition for Human Extravehicular Activity Based on Cognitive Work Analysis

PubMed Central

Miller, Matthew James; McGuire, Kerry M.; Feigh, Karen M.

2016-01-01

The design and adoption of decision support systems within complex work domains is a challenge for cognitive systems engineering (CSE) practitioners, particularly at the onset of project development. This article presents an example of applying CSE techniques to derive design requirements compatible with traditional systems engineering to guide decision support system development. Specifically, it demonstrates the requirements derivation process based on cognitive work analysis for a subset of human spaceflight operations known as extravehicular activity. The results are presented in two phases. First, a work domain analysis revealed a comprehensive set of work functions and constraints that exist in the extravehicular activity work domain. Second, a control task analysis was performed on a subset of the work functions identified by the work domain analysis to articulate the translation of subject matter states of knowledge to high-level decision support system requirements. This work emphasizes an incremental requirements specification process as a critical component of CSE analyses to better situate CSE perspectives within the early phases of traditional systems engineering design. PMID:28491008

Decision Support System Requirements Definition for Human Extravehicular Activity Based on Cognitive Work Analysis.

PubMed

Miller, Matthew James; McGuire, Kerry M; Feigh, Karen M

2017-06-01

The design and adoption of decision support systems within complex work domains is a challenge for cognitive systems engineering (CSE) practitioners, particularly at the onset of project development. This article presents an example of applying CSE techniques to derive design requirements compatible with traditional systems engineering to guide decision support system development. Specifically, it demonstrates the requirements derivation process based on cognitive work analysis for a subset of human spaceflight operations known as extravehicular activity . The results are presented in two phases. First, a work domain analysis revealed a comprehensive set of work functions and constraints that exist in the extravehicular activity work domain. Second, a control task analysis was performed on a subset of the work functions identified by the work domain analysis to articulate the translation of subject matter states of knowledge to high-level decision support system requirements. This work emphasizes an incremental requirements specification process as a critical component of CSE analyses to better situate CSE perspectives within the early phases of traditional systems engineering design.

Hepatoprotective Effect of Polyphenol-Enriched Fraction from Folium Microcos on Oxidative Stress and Apoptosis in Acetaminophen-Induced Liver Injury in Mice.

PubMed

Wu, Hongtan; Zhang, Gang; Huang, Lisen; Pang, Haiyue; Zhang, Na; Chen, Yupei; Wang, Gueyhorng

2017-01-01

Folium Microcos (FM), the leaves of Microcos paniculata L., shows various biological functions including antioxidant activity and α -glucosidase inhibitory effect. However, its therapeutic potential in acute liver injury is still unknown. This study investigated the hepatoprotective effect and underlying mechanisms of the polyphenol-enriched fraction (FMF) from Folium Microcos . FMF exhibited strong free radical scavenging activities and prevented HepG2/Hepa1-6 cells from hydrogen peroxide- (H 2 O 2 -) induced ROS production and apoptosis in vitro. Antioxidant activity and cytoprotective effects were further verified by alleviating APAP-induced hepatotoxicity in mice. Western blot analysis revealed that FMF pretreatment significantly abrogated APAP-mediated phosphorylation of MAPKs, activation of proapoptotic protein caspase-3/9 and Bax, and restored expression of antiapoptotic protein Bcl2. APAP-intoxicated mice pretreated with FMF showed increased nuclear accumulation of nuclear factor erythroid 2-related factor (Nrf2) and elevated hepatic expression of its target genes, NAD(P)H:quinine oxidoreductase 1 (NQO1) and hemeoxygenase-1(HO-1). HPLC analysis revealed the four predominantly phenolic compounds present in FMF: narcissin, isorhamnetin-3-O- β -D-glucoside, isovitexin, and vitexin. Consequently, these findings indicate that FMF possesses a hepatoprotective effect against APAP-induced hepatotoxicity mainly through dual modification of ROS/MAPKs/apoptosis axis and Nrf2-mediated antioxidant response, which may be attributed to the strong antioxidant activity of phenolic components.

Expression of Human CTP Synthetase in Saccharomyces cerevisiae Reveals Phosphorylation by Protein Kinase A*

PubMed Central

Han, Gil-Soo; Sreenivas, Avula; Choi, Mal-Gi; Chang, Yu-Fang; Martin, Shelley S.; Baldwin, Enoch P.; Carman, George M.

2005-01-01

CTP synthetase (EC 6.3.4.2, UTP: ammonia ligase (ADP-forming)) is an essential enzyme in all organisms; it generates the CTP required for the synthesis of nucleic acids and membrane phospholipids. In this work we showed that the human CTP synthetase genes, CTPS1 and CTPS2, were functional in Saccharomyces cerevisiae and complemented the lethal phenotype of the ura7Δ ura8Δ mutant lacking CTP synthetase activity. The expression of the CTPS1-and CTPS2-encoded human CTP synthetase enzymes in the ura7Δ ura8Δ mutant was shown by immunoblot analysis of CTP synthetase proteins, the measurement of CTP synthetase activity, and the synthesis of CTP in vivo. Phosphoamino acid and phosphopeptide mapping analyses of human CTP synthetase 1 isolated from 32Pi-labeled cells revealed that the enzyme was phosphorylated on multiple serine residues in vivo. Activation of protein kinase A activity in yeast resulted in transient increases (2-fold) in the phosphorylation of human CTP synthetase 1 and the cellular level of CTP. Human CTP synthetase 1 was also phosphorylated by mammalian protein kinase A in vitro. Using human CTP synthetase 1 purified from Escherichia coli as a substrate, protein kinase A activity was dose- and time-dependent, and dependent on the concentrations of CTP synthetase1 and ATP. These studies showed that S. cerevisiae was useful for the analysis of human CTP synthetase phosphorylation. PMID:16179339

A long-term epigenetic memory switch controls bacterial virulence bimodality

PubMed Central

Ronin, Irine; Katsowich, Naama; Rosenshine, Ilan; Balaban, Nathalie Q

2017-01-01

When pathogens enter the host, sensing of environmental cues activates the expression of virulence genes. Opposite transition of pathogens from activating to non-activating conditions is poorly understood. Interestingly, variability in the expression of virulence genes upon infection enhances colonization. In order to systematically detect the role of phenotypic variability in enteropathogenic E. coli (EPEC), an important human pathogen, both in virulence activating and non-activating conditions, we employed the ScanLag methodology. The analysis revealed a bimodal growth rate. Mathematical modeling combined with experimental analysis showed that this bimodality is mediated by a hysteretic memory-switch that results in the stable co-existence of non-virulent and hyper-virulent subpopulations, even after many generations of growth in non-activating conditions. We identified the per operon as the key component of the hysteretic switch. This unique hysteretic memory switch may result in persistent infection and enhanced host-to-host spreading. DOI: http://dx.doi.org/10.7554/eLife.19599.001 PMID:28178445

Structural characterization and evaluation of the antioxidant activities of polysaccharides extracted from Qingzhuan brick tea.

PubMed

Yang, Xinhe; Huang, Mingjun; Qin, Caiqin; Lv, Bangyu; Mao, Qingli; Liu, Zhonghua

2017-08-01

The crude tea polysaccharides (CTPS) from Qingzhuan brick tea(QZBT) were extracted and fractionated to afford two fractions, namely TPS-1 and TPS-2. Analyses were conducted concerning the structural characterization and antioxidant activities of these samples. Component analysis revealed that the carbohydrate, uronic acid, protein and polyphenol contents of these samples differed significantly. Fourier transform infrared analysis showed that these samples showed similar characteristic absorption peaks for polysaccharides. Ultraviolet-visible spectroscopy, circular dichroism, scanning electron microscopy and thermogravimetric analyses indicated that there were considerable differences in the presence of protein, surface features, conformational characteristics and thermodynamic behaviors. For antioxidant activities in vitro, CTPS, TPS-1 and TPS-2 exhibited concentration-dependent antioxidant activities, with TPS-2 showing significantly higher antioxidant activity than CTPS and TPS-1. These results provide a scientific and strong foundation for the use of tea polysaccharides(TPS) from QZBT and further research towards the relationships between the characteristics and antioxidant activities of TPS. Copyright © 2017 Elsevier B.V. All rights reserved.

Cytotoxic macrophage-released tumour necrosis factor-alpha (TNF-α) as a killing mechanism for cancer cell death after cold plasma activation

NASA Astrophysics Data System (ADS)

Kaushik, Nagendra Kumar; Kaushik, Neha; Min, Booki; Choi, Ki Hong; Hong, Young June; Miller, Vandana; Fridman, Alexander; Choi, Eun Ha

2016-03-01

The present study aims at studying the anticancer role of cold plasma-activated immune cells. The direct anti-cancer activity of plasma-activated immune cells against human solid cancers has not been described so far. Hence, we assessed the effect of plasma-treated RAW264.7 macrophages on cancer cell growth after co-culture. In particular, flow cytometer analysis revealed that plasma did not induce any cell death in RAW264.7 macrophages. Interestingly, immunofluorescence and western blot analysis confirmed that TNF-α released from plasma-activated macrophages acts as a tumour cell death inducer. In support of these findings, activated macrophages down-regulated the cell growth in solid cancer cell lines and induced cell death in vitro. Together our findings suggest plasma-induced reactive species recruit cytotoxic macrophages to release TNF-α, which blocks cancer cell growth and can have the potential to contribute to reducing tumour growth in vivo in the near future.

Psychometric Properties of Physical Activity and Leisure Motivation Scale in Farsi: an International Collaborative Project on Motivation for Physical Activity and Leisure.

PubMed

Zarei, Sahar; Memari, Amir-Hossein; Moshayedi, Pouria; Mosayebi, Fatolla; Mansournia, Mohammad Ali; Khoo, Selina; Morris, Tony

2016-10-01

Given the importance of regular physical activity, it is crucial to evaluate the factors favoring participation in physical activity. We aimed to report the psychometric analysis of the Farsi version of the Physical Activity and Leisure Motivation Scale (PALMS). The Farsi version of PALMS was completed by 406 healthy adult individuals to test its factor structure and concurrent validity and reliability. Conducting the exploratory factor analysis revealed nine factors that accounted for 64.6% of the variances. The PALMS reliability was supported with a high internal consistency of 0.91 and a high test-retest reliability of 0.97 (95% CI: 0.97-0.98). The association between the PALMS and its previous version Recreational Exercise Motivation Measure scores was strongly significant (r= 0.86, P < 0.001). We have shown that the Farsi version of the PALMS appears to be a valuable instrument to measure motivation for physical activity and leisure.

Multivariate statistical analysis to characterize/discriminate between anthropogenic and geogenic trace elements occurrence in the Campania Plain, Southern Italy.

PubMed

Busico, Gianluigi; Cuoco, Emilio; Kazakis, Nerantzis; Colombani, Nicolò; Mastrocicco, Micòl; Tedesco, Dario; Voudouris, Konstantinos

2018-03-01

Shallow aquifers are the most accessible reservoirs of potable groundwater; nevertheless, they are also prone to various sources of pollution and it is usually difficult to distinguish between human and natural sources at the watershed scale. The area chosen for this study (the Campania Plain) is characterized by high spatial heterogeneities both in geochemical features and in hydraulic properties. Groundwater mineralization is driven by many processes such as, geothermal activity, weathering of volcanic products and intense human activities. In such a landscape, multivariate statistical analysis has been used to differentiate among the main hydrochemical processes occurring in the area, using three different approaches of factor analysis: (i) major elements, (ii) trace elements, (iii) both major and trace elements. The elaboration of the factor analysis approaches has revealed seven distinct hydrogeochemical processes: i) Salinization (Cl - , Na + ); ii) Carbonate rocks dissolution; iii) Anthropogenic inputs (NO 3 - , SO 4 2- , U, V); iv) Reducing conditions (Fe 2+ , Mn 2+ ); v) Heavy metals contamination (Cr and Ni); vi) Geothermal fluids influence (Li + ); and vii) Volcanic products contribution (As, Rb). Results from this study highlight the need to separately apply factor analysis when a large data set of trace elements is available. In fact, the impact of geothermal fluids in the shallow aquifer was identified from the application of the factor analysis using only trace elements. This study also reveals that the factor analysis of major and trace elements can differentiate between anthropogenic and geogenic sources of pollution in intensively exploited aquifers. Copyright © 2017 Elsevier Ltd. All rights reserved.

Faculty experiences teaching Native Americans in a university setting.

PubMed

Dickerson, S S; Neary, M A

1999-01-01

Nursing faculty told their stories about the beginnings of a Native American Family Nurse Practitioner Recruitment Program. Through hermeneutical analysis, the authors' findings reveal a strong academic worldview, active in maintaining professional standards. This traditional view tends to override efforts to provide individualized programs that are culturally relevant to the Native American worldviews. By understanding the value conflicts active in this study, nursing faculty can begin dialogue to create new learning experiences that are more culturally relevant.

Cystamine immobilization on TiO 2 film surfaces and the influence on inhibition of collagen-induced platelet activation

NASA Astrophysics Data System (ADS)

Zhou, Yujuan; Weng, Yajun; Zhang, Liping; Jing, Fengjuan; Huang, Nan; Chen, Junying

2011-12-01

Poor haemocompatibility is a main issue of artificial cardiovascular materials in clinical application. Nitric oxide (NO), produced by vascular endothelial cells, is a well known inhibitor of platelet adhesion and activation. Thus, NO-releasing biomaterials are beneficial for improving haemocompatibility of blood-contacting biomedical devices. In this paper, a novel method was developed for enhancement of haemocompatibility by exploiting endogenous NO donors. TiO 2 films were firstly synthesized on Si (1 0 0) wafers via unbalanced magnetron sputtering technology, and then polydopamine was grafted on TiO 2 films and used as a linker for further immobilization of cystamine. The obtained surfaces were characterized by scanning electron microscope (SEM), Fourier transform infrared spectroscopy (FTIR) and X-ray photoelectron spectroscopy (XPS) analysis. NO generation is evaluated by saville-griess reagents, and it shows that cystamine immobilized samples are able to catalytically generate NO by decomposing endogenous S-nitrosothiols (RSNO). In vitro platelet adhesion results reveal that cystamine modified surfaces can inhibit collagen-induced platelet activation. ELISA analysis reveals that cGMP in platelets obviously increases on cystamine immobilized surface, which suggests the reducing of platelet activation is through NO/cGMP signal channel. It can be concluded that cystamine immobilized surface shows better blood compatibility by catalyzing NO release from the endogenous NO donor. It may be a promising method for improvement of haemocompatibility of blood-contacting implants.

Extracellular proteases from Streptomyces phaeopurpureus ExPro138 inhibit spore adhesion, germination and appressorium formation in Colletotrichum coccodes.

PubMed

Palaniyandi, S A; Yang, S H; Suh, J-W

2013-07-01

To study the antifungal mechanism of proteases from Streptomyces phaeopurpureus strain ExPro138 towards Colletotrichum coccodes and to evaluate its utilization as biofungicide. We screened proteolytic Streptomyces strains from the yam rhizosphere with antifungal activity. Forty proteolytic Streptomyces were isolated, among which eleven isolates showed gelatinolytic activity and antagonistic activity on C. coccodes. Of the 11 isolates, protease preparation from an isolate designated ExPro138 showed antifungal activity. 16S rDNA sequence analysis of the strain showed 99% similarity with Streptomyces phaeopurepureus (EU841588.1). Zymography analysis of the ExPro138 culture filtrate revealed that the strain produced several extracellular proteases. The protease preparation inhibited spore germination, spore adhesion to polystyrene surface and appressorium formation. Microscopic study of the interaction between ExPro138 and C. coccodes revealed that ExPro138 was mycoparasitic on C. coccodes. The protease preparation also reduced anthracnose incidence on tomato fruits compared with untreated control. This study demonstrates possibility of utilizing antifungal proteases derived from antagonistic microbes as biofungicide. Microbial proteases having the ability to inhibit spore adhesion and appressorium formation could be used to suppress infection establishment by foliar fungal pathogens at the initial stages of the infection process. Journal of Applied Microbiology © 2013 The Society for Applied Microbiology.

Insight into Genotype-Phenotype Associations through eQTL Mapping in Multiple Cell Types in Health and Immune-Mediated Disease

PubMed Central

Peters, James E.; Lyons, Paul A.; Lee, James C.; Richard, Arianne C.; Fortune, Mary D.; Newcombe, Paul J.; Richardson, Sylvia; Smith, Kenneth G. C.

2016-01-01

Genome-wide association studies (GWAS) have transformed our understanding of the genetics of complex traits such as autoimmune diseases, but how risk variants contribute to pathogenesis remains largely unknown. Identifying genetic variants that affect gene expression (expression quantitative trait loci, or eQTLs) is crucial to addressing this. eQTLs vary between tissues and following in vitro cellular activation, but have not been examined in the context of human inflammatory diseases. We performed eQTL mapping in five primary immune cell types from patients with active inflammatory bowel disease (n = 91), anti-neutrophil cytoplasmic antibody-associated vasculitis (n = 46) and healthy controls (n = 43), revealing eQTLs present only in the context of active inflammatory disease. Moreover, we show that following treatment a proportion of these eQTLs disappear. Through joint analysis of expression data from multiple cell types, we reveal that previous estimates of eQTL immune cell-type specificity are likely to have been exaggerated. Finally, by analysing gene expression data from multiple cell types, we find eQTLs not previously identified by database mining at 34 inflammatory bowel disease-associated loci. In summary, this parallel eQTL analysis in multiple leucocyte subsets from patients with active disease provides new insights into the genetic basis of immune-mediated diseases. PMID:27015630

The tryptophan-derived endogenous arylhydrocarbon receptor ligand 6-formylindolo[3,2-b]carbazole (FICZ) is a nanomolar UVA-photosensitizer in epidermal keratinocytes

PubMed Central

Williams, Joshua D.; Cabello, Christopher M.; Qiao, Shuxi; Wondrak, Georg T.

2014-01-01

Endogenous UVA-chromophores may act as sensitizers of oxidative stress underlying cutaneous photoaging and photocarcinogenesis, but the molecular identity of non-DNA key chromophores displaying UVA-driven photodyamic activity in human skin remains largely undefined. Here we report that 6-formylindolo[3,2-b]carbazole (FICZ), a tryptophan photoproduct and endogenous high affinity aryl hydrocarbon receptor (AhR) agonist, acts as a nanomolar photosensitizer potentiating UVA-induced oxidative stress irrespective of AhR ligand activity. In human HaCaT and primary epidermal keratinocytes, photodynamic induction of apoptosis was elicited by the combined action of solar simulated UVA and FICZ, whereas exposure to the isolated action of UVA or FICZ did not impair viability. In a human epidermal tissue reconstruct, FICZ/UVA-cotreatment caused pronounced phototoxicity inducing keratinocyte cell death, and FICZ photodynamic activity was also substantiated in a murine skin exposure model. Array analysis revealed pronounced potentiation of cellular heat shock, ER stress, and oxidative stress response gene expression observed only upon FICZ/UVA-cotreatment. FICZ photosensitization caused intracellular oxidative stress, and comet analysis revealed introduction of formamidopyrimidine-DNA glycosylase (FPG)-sensitive oxidative DNA lesions suppressible by antioxidant cotreatment. Taken together, our data demonstrate that the endogenous AhR ligand FICZ displays nanomolar photodynamic activity representing a molecular mechanism of UVA-induced photooxidative stress potentially operative in human skin. PMID:25431849

Purification of adult hepatic progenitor cells using green fluorescent protein (GFP)-transgenic mice and fluorescence-activated cell sorting.

PubMed

Fujikawa, Takahisa; Hirose, Tetsuro; Fujii, Hideaki; Oe, Shoshiro; Yasuchika, Kentaro; Azuma, Hisaya; Yamaoka, Yoshio

2003-08-01

Recent advances in stem cell research have revealed that hepatic stem/progenitor cells may play an important role in liver development and regeneration. However, a lack of detectable definitive markers in viable cells has hindered their primary culture from adult livers. Enzymatically dissociated liver cells from green fluorescent protein (GFP)-transgenic mice, which express GFP highly in liver endodermal cells, were sorted by GFP expression using a fluorescence-activated cell sorter. Sorted cells were characterized, and also low-density cultured for extended periods to determine their proliferation and clonal differentiation capacities. When CD45(-)TER119(-) side-scatter(low) GFP(high) cells were sorted, alpha-fetoprotein-positive immature endoderm-characterized cells, having high growth potential, were present in this population. Clonal analysis and electron microscopic evaluation revealed that each single cell of this population could differentiate not only into hepatocytes, but also into biliary epithelial cells, showing their bilineage differentiation activity. When surface markers were analyzed, they were positive for Integrin-alpha6 and -beta1, but negative for c-Kit and Thy1.1. Combination of GFP-transgenic mice and fluorescence-activated cell sorting enabled purification of hepatic progenitor cells from adult mouse liver. Further analysis of this population may lead to purification of their human correspondence that would be an ideal cell-source candidate for regenerative medicine.

Modular synthesis and in vitro and in vivo antimalarial assessment of C-10 pyrrole mannich base derivatives of artemisinin.

PubMed

Pacorel, Bénédicte; Leung, Suet C; Stachulski, Andrew V; Davies, Jill; Vivas, Livia; Lander, Hollie; Ward, Stephen A; Kaiser, Marcel; Brun, Reto; O'Neill, Paul M

2010-01-28

In two steps from dihydroartemisinin, a small array of 16 semisynthetic C-10 pyrrole Mannich artemisinin derivatives (7a-p) have been prepared in moderate to excellent yield. In vitro analysis against both chloroquine sensitive and resistant strains has demonstrated that these analogues have nanomolar antimalarial activity, with several compounds being more than 3 times more potent than the natural product artemisinin. In addition to a potent antimalarial profile, these molecules also have very high in vitro therapeutic indices. Analysis of the optimal Mannich side chain substitution for in vitro and in vivo activity reveals that the morpholine and N-methylpiperazine Mannich side chains provide analogues with the best activity profiles, both in vitro and in vivo in the Peter's 4 day test.

Dinardokanshones C-E, isonardoeudesmols A-D and nardoeudesmol D from Nardostachys jatamansi DC.

PubMed

Wu, Hong-Hua; Deng, Xu; Zhang, Hu; Chen, Ying-Peng; Ying, Shu-Song; Wu, Yi-Jing; Liu, Yan-Ting; Zhu, Yan; Gao, Xiu-Mei; Xu, Yan-Tong; Li, Li

2018-06-01

Dinardokanshones C-E, three sesquiterpenoid dimers comprising an unusual nornardosinane-type sesquiterpenoid core and an aristolane-type sesquiterpenoid unit conjugated by an extra pyran or furan ring, together with monomeric sesquiterpenoids isonardoeudesmols A-D and nardoeudesmol D, were isolated from the underground parts of Nardostachys jatamansi DC. Structures of the eight compounds were elucidated by analysis of the extensive spectroscopic data, and their absolute configurations were established by analysis of NOESY and X-ray diffraction data, combined with computational electronic circular dichroism (ECD) calculations. The results of SERT activity assay revealed that isonardoeudesmol D and nardoeudesmol D significantly inhibited SERT activity, while dinardokanshones D-E and isonardoeudesmols B-C significantly enhanced SERT activity, among which dinardokanshone D exhibited the strongest effect. Copyright © 2018 Elsevier Ltd. All rights reserved.

Identification of Surface Water Quality along the Coast of Sanya, South China Sea

PubMed Central

Wu, Zhen-Zhen; Che, Zhi-Wei; Wang, You-Shao; Dong, Jun-De; Wu, Mei-Lin

2015-01-01

Principal component analysis (PCA) and cluster analysis (CA) are utilized to identify the effects caused by human activities on water quality along the coast of Sanya, South China Sea. PCA and CA identify the seasonality of water quality (dry and wet seasons) and polluted status (polluted area). The seasonality of water quality is related to climate change and Southeast monsoons. Spatial pattern is mainly related to anthropogenic activities (especially land input of pollutions). PCA reveals the characteristics underlying the generation of coastal water quality. The temporal and spatial variation of the trophic status along the coast of Sanya is governed by hydrodynamics and human activities. The results provide a novel typological understanding of seasonal trophic status in a shallow, tropical, open marine bay. PMID:25894980

Spectral investigations, DFT computations and molecular docking studies of 1,7,8,9-tetrachloro-10,10-dimethoxy-4-{3-[4-(2-methylphenyl)piperazin-1-yl]propyl}-4-azatricyclo[5.2.1.02,6]dec-8-ene-3,5-dione

NASA Astrophysics Data System (ADS)

Resmi, K. S.; Mary, Y. Sheena; Varghese, Hema Tresa; Panicker, C. Yohannan; Pakosińska-Parys, Magdalena; Alsenoy, C. Van

2015-10-01

The optimized molecular structure, vibrational frequencies, corresponding vibrational assignments of the title compound have been investigated experimentally and theoretically. The HOMO and LUMO analysis is used to determine the charge transfer within the molecule. The stability of the molecule arising from hyper-conjugative interaction and charge delocalization has been analysed using NBO analysis. The hyperpolarisability calculation reveals the present material has a reasonably good propensity for nonlinear optical activity. Due to the different potential biological activity of the title compound, molecular docking study is also reported and the compound might exhibit inhibitory activity against human M2 muscarinic acetylcholine receptor.

Genome-wide transcriptional analysis of flagellar regeneration in Chlamydomonas reinhardtii identifies orthologs of ciliary disease genes

NASA Technical Reports Server (NTRS)

Stolc, Viktor; Samanta, Manoj Pratim; Tongprasit, Waraporn; Marshall, Wallace F.

2005-01-01

The important role that cilia and flagella play in human disease creates an urgent need to identify genes involved in ciliary assembly and function. The strong and specific induction of flagellar-coding genes during flagellar regeneration in Chlamydomonas reinhardtii suggests that transcriptional profiling of such cells would reveal new flagella-related genes. We have conducted a genome-wide analysis of RNA transcript levels during flagellar regeneration in Chlamydomonas by using maskless photolithography method-produced DNA oligonucleotide microarrays with unique probe sequences for all exons of the 19,803 predicted genes. This analysis represents previously uncharacterized whole-genome transcriptional activity profiling study in this important model organism. Analysis of strongly induced genes reveals a large set of known flagellar components and also identifies a number of important disease-related proteins as being involved with cilia and flagella, including the zebrafish polycystic kidney genes Qilin, Reptin, and Pontin, as well as the testis-expressed tubby-like protein TULP2.

Purine analogue ENERGI-F706 induces apoptosis of 786-O renal carcinoma cells via 5'-adenosine monophosphate-activated protein kinase activation.

PubMed

Hsu, Chao-Yu; Lin, Chun-Hsiang; Lin, Jiun-Tsai; Cheng, Yi-Fang; Chen, Han-Min; Kao, Shao-Hsuan

2015-09-01

Purine compounds are known to activate 5'-adenosine monophosphate-activated protein kinase (AMPK), which has important roles in treatments for renal cell carcinoma. The present study was aimed to investigate the effects of the purine analogue ENERGI‑F706 on the human renal carcinoma cell line 786‑O and the underlying mechanisms. The results revealed that ENERGI‑F706 (0.2‑0.6 mg/ml) significantly decreased the cell viability to up to 36.4±2.4% of that of the control. Compared to 786‑O cells, ENERGI‑F706 exerted less suppressive effects on the viability of the human non‑tumorigenic renal cell line HK‑2. Flow cytometric analysis showed that ENERGI‑F706 contributed to cell cycle arrest at S‑phase and triggered apoptosis of 786‑O cells. Immunoblot analysis revealed that anti‑apoptotic B‑cell lymphoma 2 (Bcl‑2) levels were reduced and pro‑apoptotic Bcl‑2‑associated X protein levels were diminished. In addition, activation of caspase‑9, caspase‑3 and poly(adenosine diphosphate ribose) polymerase (PARP) was promoted in 786‑O cells in response to ENERGI‑F706. Effects of ENERGI‑F706 on AMPK cascades were investigated and the results showed that ENERGI‑F706 enhanced phosphorylation of AMPKα (T172) and p53 (S15), a downstream target of AMPK. In addition, the AMPK activation, p53 (S15) phosphorylation, reduction of Bcl‑2, cleavage of caspase‑3 and PARP as well as suppressed cell viability induced by ENERGI‑F706 were reversed in the presence of AMPK inhibitor compound C (dorsomorphin). In conclusion, the findings of the present study revealed that ENERGI‑F706 significantly suppressed the viability of 786‑O cells via induction of cell cycle arrest and apoptosis, attributing to AMPK and p53 activation and subsequent cell cycle regulatory and apoptotic signaling. It was therefore indicated that ENERGI‑F706 may be suitable for the treatment of renal cell carcinoma.

Alteration of matrix metalloproteinase-3 O-glycan structure as a biomarker for disease activity of rheumatoid arthritis.

PubMed

Takeshita, Masaru; Kuno, Atsushi; Suzuki, Katsuya; Matsuda, Atsushi; Shimazaki, Hiroko; Nakagawa, Tomomi; Otomo, Yuki; Kabe, Yasuaki; Suematsu, Makoto; Narimatsu, Hisashi; Takeuchi, Tsutomu

2016-05-21

Nearly all secreted proteins are glycosylated, and serum glycoproteins that exhibit disease-associated glycosylation changes have potential to be biomarkers. In rheumatoid arthritis (RA), C-reactive protein (CRP), and matrix metalloproteinase-3 (MMP-3) are widely used as serologic biomarkers, but they lack sufficient specificity or precision. We performed comparative glycosylation profiling of MMP-3 using a recently developed antibody-overlay lectin microarray technology that allows semicomprehensive and quantitative analysis of specific protein glycosylation to develop an RA-specific disease activity biomarker. Serum was taken from patients with RA (n = 24) whose disease activity was scored using composite measures, and MMP-3 was immunoprecipitated and subjected to lectin microarray analysis. A disease activity index (DAI) based on lectin signal was developed and validated using another cohort (n = 60). Synovial fluid MMP-3 in patients with RA and patients with osteoarthritis (OA) was also analyzed. Intense signals were observed on a sialic acid-binding lectin (Agrocybe cylindracea galectin [ACG]) and O-glycan-binding lectins (Jacalin, Agaricus bisporus agglutinin [ABA], and Amaranthus caudatus agglutinin [ACA]) by applying subnanogram levels of serum MMP-3. ACG, ABA, and ACA revealed differences in MMP-3 quantity, and Jacalin revealed differences in MMP-3 quality. The resultant index, ACG/Jacalin, correlated well with disease activity. Further validation using another cohort confirmed that this index correlated well with several DAIs and their components, and reflected DAI changes following RA treatment, with correlations greater than those for MMP-3 and CRP. Furthermore, MMP-3, which generated a high ACG/Jacalin score, accumulated in synovial fluid of patients with RA but not in that of patients with OA. Sialidase digestion revealed that the difference in quality was derived from O-glycan α-2,6-sialylation. This is the first report of a glycoprotein biomarker using glycan change at a local lesion to assess disease activity in autoimmune diseases. Differences in the degree of serum MMP-3 α-2,6-sialylation may be a useful index for estimating disease activity.

Focal complex formation in adult cardiomyocytes is accompanied by the activation of beta3 integrin and c-Src.

PubMed

Willey, Christopher D; Balasubramanian, Sundaravadivel; Rodríguez Rosas, María C; Ross, Robert S; Kuppuswamy, Dhandapani

2003-06-01

In pressure-overloaded myocardium, our recent study demonstrated cytoskeletal assembly of c-Src and other signaling proteins which was partially mimicked in vitro using adult feline cardiomyocytes embedded in three-dimensional (3D) collagen matrix and stimulated with an integrin-binding Arg-Gly-Asp (RGD) peptide. In the present study, we improved this model further to activate c-Src and obtain a full assembly of the focal adhesion complex (FAC), and characterized c-Src localization and integrin subtype(s) involved. RGD dose response experiments revealed that c-Src activation occurs subsequent to its cytoskeletal recruitment and is accompanied by p130Cas cytoskeletal binding and focal adhesion kinase (FAK) Tyr925 phosphorylation. When cardiomyocytes expressing hexahistidine-tagged c-Src via adenoviral gene delivery were used for RGD stimulation, the expressed c-Src exhibited relocation: (i) biochemical analysis revealed c-Src movement from the detergent-soluble to the -insoluble cytoskeletal fraction and (ii) confocal microscopic analysis showed c-Src movement from a nuclear/perinuclear to a sarcolemmal region. RGD treatment also caused sarcolemmal co-localization of FAK and vinculin. Characterization of integrin subtypes revealed that beta3, but not beta1, integrin plays a predominant role: (i) expression of cytoplasmic domain of beta1A integrin did not affect the RGD-stimulated FAC formation and (ii) both pressure-overloaded myocardium and RGD-stimulated cardiomyocytes exhibited phosphorylation of beta3 integrin at Tyr773/785 sites but not beta1 integrin at Thr788/789 sites. Together these data indicate that RGD treatment in cardiomyocytes causes beta3 integrin activation and c-Src sarcolemmal localization, that subsequent c-Src activation is accompanied by p130Cas binding and FAK Tyr925 phosphorylation, and that these events might be crucial for growth and remodeling of hypertrophying adult cardiomyocytes.

Pseudoprogression manifesting as recurrent ascites with anti-PD-1 immunotherapy in urothelial bladder cancer.

PubMed

Sweis, Randy F; Zha, Yuanyuan; Pass, Lomax; Heiss, Brian; Chongsuwat, Tara; Luke, Jason J; Gajewski, Thomas F; Szmulewitz, Russell

2018-04-04

Immunotherapies targeting the PD-1 checkpoint pathway have recently gained regulatory approval in numerous cancer types. With the widespread use of immune checkpoint therapies, varying patterns of responses and immune-related adverse events are being observed. In this case, we highlight a patient who developed recurrent, large-volume ascites, while simultaneously having a 49% reduction in peritoneal tumor lesion size by RECIST criteria. Sampling of the fluid revealed high levels of IL-6 and IL-15. Cytology revealed no malignant cells on 4 separate paracenteses over a period of 6 weeks. Cell counts revealed that 45% of cells were lymphocytes, and further analysis was performed by fluorescence-activated cell sorting (FACS). The majority of lymphocytes were CD8 + , of which 78% were PD-1 + and 43% were HLA-DR + indicating an activated phenotype. In summary, treatment with anti-PD-1 therapy may result in pseudoprogression manifested by ascitic fluid accumulation due to the influx of activated T cells. Since worsening of ascites is typically associated with disease progression, it is important to consider the possibility of pesudoprogression in such patients undergoing therapy with immune checkpoint inhibitors.

Fibrinolytic, anti-inflammatory and anti-microbial properties of α-(1-3)-glucans produced from Streptococcus mutans (MTCC 497).

PubMed

Buddana, Sudheer Kumar; Varanasi, Yaswanth Venkata Naga; Shetty, Prakasham Reddy

2015-01-22

Streptococcus mutans (MTCC 497) cell associated α-(1-3)-glucans were isolated, characterized and evaluated for their bioactivity profile. Acid hydrolysis of α-(1-3)-glucans revealed presence of glucose moieties. Water insoluble α-(1-3)-glucans (WIG) were sulfated to convert them into water soluble glucans which were characterized by FT-IR spectral studies. The sulfation of WIG was confirmed by the presence of -O-SO3- and C-O-SO3- characteristic peaks at 1240 and 820 cm(-1). MALDI-TOF analysis of sulfated α-(1-3)-glucan revealed 1.2 to 9kDa fragmentation. Antibacterial profile studies revealed higher growth inhibitory activity against Gram negative than Gram positive bacterial strains by sulfated α-(1-3)-glucans. One-fold higher anti-inflammatory activity with IC50 value of 0.11mg/ml was observed with sulfated α-(1-3)-glucans over WIG. Time dependent fibrinolytic potential without requirement of tissue plasminogen activators was observed for sulfated α-(1-3)-glucans. This is the first report demonstrating the fibrinolytic and anti-inflammatory property for sulfated α-(1-3)-glucans. Copyright © 2014 Elsevier Ltd. All rights reserved.

The influence of human physical activity and contaminated clothing type on particle resuspension.

PubMed

McDonagh, A; Byrne, M A

2014-01-01

A study was conducted to experimentally quantify the influence of three variables on the level of resuspension of hazardous aerosol particles from clothing. Variables investigated include physical activity level (two levels, low and high), surface type (four different clothing material types), and time i.e. the rate at which particles resuspend. A mixture of three monodisperse tracer-labelled powders, with median diameters of 3, 5, and 10 microns, was used to "contaminate" the samples, and the resuspended particles were analysed in real-time using an Aerodynamic Particle Sizer (APS), and also by Neutron Activation Analysis (NAA). The overall finding was that physical activity resulted in up to 67% of the contamination deposited on clothing being resuspended back into the air. A detailed examination of the influence of physical activity level on resuspension, from NAA, revealed that the average resuspended fraction (RF) of particles at low physical activity was 28 ± 8%, and at high physical activity was 30 ± 7%, while the APS data revealed a tenfold increase in the cumulative mass of airborne particles during high physical activity in comparison to that during low physical activity. The results also suggest that it is not the contaminated clothing's fibre type which influences particle resuspension, but the material's weave pattern (and hence the material's surface texture). Investigation of the time variation in resuspended particle concentrations indicated that the data were separable into two distinct regimes: the first (occurring within the first 1.5 min) having a high, positive rate of change of airborne particle concentration relative to the second regime. The second regime revealed a slower rate of change of particle concentration and remained relatively unchanged for the remainder of each resuspension event. Copyright © 2013 Elsevier Ltd. All rights reserved.

The brain in time: insights from neuromagnetic recordings.

PubMed

Hari, Riitta; Parkkonen, Lauri; Nangini, Cathy

2010-03-01

The millisecond time resolution of magnetoencephalography (MEG) is instrumental for investigating the brain basis of sensory processing, motor planning, cognition, and social interaction. We review the basic principles, recent progress, and future potential of MEG in noninvasive tracking of human brain activity. Cortical activation sequences from tens to hundreds of milliseconds can be followed during, e.g., perception, motor action, imitation, and language processing by recording both spontaneous and evoked brain signals. Moreover, tagging of sensory input can be used to reveal neuronal mechanisms of binaural interaction and perception of ambiguous images. The results support the emerging ideas of multiple, hierarchically organized temporal scales in human brain function. Instrumentation and data analysis methods are rapidly progressing, enabling attempts to decode the four-dimensional spatiotemporal signal patterns to reveal correlates of behavior and mental contents.

Impaired social brain network for processing dynamic facial expressions in autism spectrum disorders

PubMed Central

2012-01-01

Background Impairment of social interaction via facial expressions represents a core clinical feature of autism spectrum disorders (ASD). However, the neural correlates of this dysfunction remain unidentified. Because this dysfunction is manifested in real-life situations, we hypothesized that the observation of dynamic, compared with static, facial expressions would reveal abnormal brain functioning in individuals with ASD. We presented dynamic and static facial expressions of fear and happiness to individuals with high-functioning ASD and to age- and sex-matched typically developing controls and recorded their brain activities using functional magnetic resonance imaging (fMRI). Result Regional analysis revealed reduced activation of several brain regions in the ASD group compared with controls in response to dynamic versus static facial expressions, including the middle temporal gyrus (MTG), fusiform gyrus, amygdala, medial prefrontal cortex, and inferior frontal gyrus (IFG). Dynamic causal modeling analyses revealed that bi-directional effective connectivity involving the primary visual cortex–MTG–IFG circuit was enhanced in response to dynamic as compared with static facial expressions in the control group. Group comparisons revealed that all these modulatory effects were weaker in the ASD group than in the control group. Conclusions These results suggest that weak activity and connectivity of the social brain network underlie the impairment in social interaction involving dynamic facial expressions in individuals with ASD. PMID:22889284

Bi-phasic activation of the primary motor cortex by pain and its relation to pain-evoked potentials - an exploratory study.

PubMed

Kisler, Lee-Bareket; Weissman-Fogel, Irit; Sinai, Alon; Sprecher, Elliot; Chistyakov, Andrei V; Shamay-Tsoory, Simone; Moscovitz, Nadav; Granovsky, Yelena

2017-06-15

The primary motor cortex (M1) is a known target for brain stimulation aimed at pain alleviation in chronic pain patients, yet the mechanisms through which analgesia occurs, and the exact pain-motor interrelations are not fully understood. We used noxious contact heat evoked potentials (CHEPs) and cortical source analysis to further explore the relevance of M1 in pain processing. Twenty-four healthy young females received brief noxious heat stimuli to their left non-dominant volar forearm, simultaneously with CHEPs recordings. Thereafter, the pain-evoked activity of M1 and a control area in the occipital cortex (OC) was analyzed and estimated using sLORETA (standardized low-resolution brain electromagnetic tomography). This analysis revealed two phases of M1 pain-evoked activation (phase 1: the peak at 261.5±25.7ms; phase 2: the peak at 381.3±28.3ms). Canonical correlations revealed that M1, but not the OC, was the main factor contributing to the relation with the CHEPs components. In detail, the activity magnitude of M1 first and second phases was related to the N2 and P2 amplitude, respectively. The latency of the second phase was associated with both N2 and P2 latencies. In relation to pain, the latency of M1's first activity phase was positively correlated with pain ratings, suggesting pain interference to synchronized activity in M1. Our results confirm the established relevance of the primary motor cortex to pain processing. Copyright © 2017 Elsevier B.V. All rights reserved.

Leveraging electronic health record documentation for Failure Mode and Effects Analysis team identification

PubMed Central

Carson, Matthew B; Lee, Young Ji; Benacka, Corrine; Mutharasan, R. Kannan; Ahmad, Faraz S; Kansal, Preeti; Yancy, Clyde W; Anderson, Allen S; Soulakis, Nicholas D

2017-01-01

Objective: Using Failure Mode and Effects Analysis (FMEA) as an example quality improvement approach, our objective was to evaluate whether secondary use of orders, forms, and notes recorded by the electronic health record (EHR) during daily practice can enhance the accuracy of process maps used to guide improvement. We examined discrepancies between expected and observed activities and individuals involved in a high-risk process and devised diagnostic measures for understanding discrepancies that may be used to inform quality improvement planning. Methods: Inpatient cardiology unit staff developed a process map of discharge from the unit. We matched activities and providers identified on the process map to EHR data. Using four diagnostic measures, we analyzed discrepancies between expectation and observation. Results: EHR data showed that 35% of activities were completed by unexpected providers, including providers from 12 categories not identified as part of the discharge workflow. The EHR also revealed sub-components of process activities not identified on the process map. Additional information from the EHR was used to revise the process map and show differences between expectation and observation. Conclusion: Findings suggest EHR data may reveal gaps in process maps used for quality improvement and identify characteristics about workflow activities that can identify perspectives for inclusion in an FMEA. Organizations with access to EHR data may be able to leverage clinical documentation to enhance process maps used for quality improvement. While focused on FMEA protocols, findings from this study may be applicable to other quality activities that require process maps. PMID:27589944

Silver oxide nanoparticles embedded silk fibroin spuns: Microwave mediated preparation, characterization and their synergistic wound healing and anti-bacterial activity.

PubMed

Babu, Punuri Jayasekhar; Doble, Mukesh; Raichur, Ashok M

2018-03-01

The synergistic wound healing and antibacterial activity of silver oxide nanoparticles embedded silk fibroin (Ag 2 O-SF) spuns is reported here. UV-Vis spectro photometric analysis of these spuns showed the surface plasmon resonance (SPR) confirming the formation of the silver oxide nanoparticles (Ag 2 O NPs) on the surface of the silk fibroin (SF). Scanning electron microscope (SEM) and Differential scanning calorimetry (DSC) also confirmed the presence of Ag 2 O NPs on surface of SF. X-ray diffraction (XRD) analysis revealed the crystalline nature of both SF and Ag 2 O-SF. Fourier transform infrared spectroscopy (FT-IR) results showed the different forms of silk (I and II) and their corresponding protein (amide I, II, III) confirmations. Biodegradation study revealed insignificant changes in the morphology of Ag 2 O-SF spuns even after 14 days of immersion in phosphate buffered saline (PBS). Ag 2 O-SF spuns showed excellent antibacterial activity against both pathogen (S. aureus and M. tuberculosis) and non-pathogen (E. coli) bacteria. More importantly, In vitro wound healing (scratch assay) assay revealed fast migration of the T3T fibroblast cells through the scratch area treated with extract of Ag 2 O-SF spuns and the area was completely covered within 24 h. Cytotoxicity assay confirmed the biocompatible nature of the Ag 2 O-SF spuns, thus suggesting an ideal material for wound healing and anti-bacterial applications. Copyright © 2017 Elsevier Inc. All rights reserved.

Effect of glycyrrhetinic acid on lipid raft model at the air/water interface.

PubMed

Sakamoto, Seiichi; Uto, Takuhiro; Shoyama, Yukihiro

2015-02-01

To investigate an interfacial behavior of the aglycon of glycyrrhizin (GC), glycyrrhetinic acid (GA), with a lipid raft model consisting of equimolar ternary mixtures of N-palmitoyl sphingomyelin (PSM), dioleoylphosphatidylcholine (DOPC), and cholesterol (CHOL), Langmuir monolayer techniques were systematically conducted. Surface pressure (π)-molecular area (A) and surface potential (ΔV)-A isotherms showed that the adsorbed GA at the air/water interface was desorbed into the bulk upon compression of the lipid monolayer. In situ morphological analysis by Brewster angle microscopy and fluorescence microscopy revealed that the raft domains became smaller as the concentrations of GA in the subphase (CGA) increased, suggesting that GA promotes the formation of fluid networks related to various cellular processes via lipid rafts. In addition, ex situ morphological analysis by atomic force microscopy revealed that GA interacts with lipid raft by lying down at the surface. Interestingly, the distinctive striped regions were formed at CGA=5.0 μM. This phenomenon was observed to be induced by the interaction of CHOL with adsorbed GA and is involved in the membrane-disrupting activity of saponin and its aglycon. A quantitative comparison of GA with GC (Sakamoto et al., 2013) revealed that GA interacts more strongly with the raft model than GC in the monolayer state. Various biological activities of GA are known to be stronger than those of GC. This fact allows us to hypothesize that differences in the interactions of GA/GC with the model monolayer correlate to their degree of exertion for numerous activities. Copyright © 2014 Elsevier B.V. All rights reserved.

Genomics-enabled analysis of the emergent disease cotton bacterial blight

PubMed Central

Phillips, Anne Z.; Burke, Jillian; Bunn, J. Imani; Allen, Tom W.; Wheeler, Terry

2017-01-01

Cotton bacterial blight (CBB), an important disease of (Gossypium hirsutum) in the early 20th century, had been controlled by resistant germplasm for over half a century. Recently, CBB re-emerged as an agronomic problem in the United States. Here, we report analysis of cotton variety planting statistics that indicate a steady increase in the percentage of susceptible cotton varieties grown each year since 2009. Phylogenetic analysis revealed that strains from the current outbreak cluster with race 18 Xanthomonas citri pv. malvacearum (Xcm) strains. Illumina based draft genomes were generated for thirteen Xcm isolates and analyzed along with 4 previously published Xcm genomes. These genomes encode 24 conserved and nine variable type three effectors. Strains in the race 18 clade contain 3 to 5 more effectors than other Xcm strains. SMRT sequencing of two geographically and temporally diverse strains of Xcm yielded circular chromosomes and accompanying plasmids. These genomes encode eight and thirteen distinct transcription activator-like effector genes. RNA-sequencing revealed 52 genes induced within two cotton cultivars by both tested Xcm strains. This gene list includes a homeologous pair of genes, with homology to the known susceptibility gene, MLO. In contrast, the two strains of Xcm induce different clade III SWEET sugar transporters. Subsequent genome wide analysis revealed patterns in the overall expression of homeologous gene pairs in cotton after inoculation by Xcm. These data reveal important insights into the Xcm-G. hirsutum disease complex and strategies for future development of resistant cultivars. PMID:28910288

Deconvoluting Post-Transplant Immunity: Cell Subset-Specific Mapping Reveals Pathways for Activation and Expansion of Memory T, Monocytes and B Cells

PubMed Central

Grigoryev, Yevgeniy A.; Kurian, Sunil M.; Avnur, Zafi; Borie, Dominic; Deng, Jun; Campbell, Daniel; Sung, Joanna; Nikolcheva, Tania; Quinn, Anthony; Schulman, Howard; Peng, Stanford L.; Schaffer, Randolph; Fisher, Jonathan; Mondala, Tony; Head, Steven; Flechner, Stuart M.; Kantor, Aaron B.; Marsh, Christopher; Salomon, Daniel R.

2010-01-01

A major challenge for the field of transplantation is the lack of understanding of genomic and molecular drivers of early post-transplant immunity. The early immune response creates a complex milieu that determines the course of ensuing immune events and the ultimate outcome of the transplant. The objective of the current study was to mechanistically deconvolute the early immune response by purifying and profiling the constituent cell subsets of the peripheral blood. We employed genome-wide profiling of whole blood and purified CD4, CD8, B cells and monocytes in tandem with high-throughput laser-scanning cytometry in 10 kidney transplants sampled serially pre-transplant, 1, 2, 4, 8 and 12 weeks. Cytometry confirmed early cell subset depletion by antibody induction and immunosuppression. Multiple markers revealed the activation and proliferative expansion of CD45RO+CD62L− effector memory CD4/CD8 T cells as well as progressive activation of monocytes and B cells. Next, we mechanistically deconvoluted early post-transplant immunity by serial monitoring of whole blood using DNA microarrays. Parallel analysis of cell subset-specific gene expression revealed a unique spectrum of time-dependent changes and functional pathways. Gene expression profiling results were validated with 157 different probesets matching all 65 antigens detected by cytometry. Thus, serial blood cell monitoring reflects the profound changes in blood cell composition and immune activation early post-transplant. Each cell subset reveals distinct pathways and functional programs. These changes illuminate a complex, early phase of immunity and inflammation that includes activation and proliferative expansion of the memory effector and regulatory cells that may determine the phenotype and outcome of the kidney transplant. PMID:20976225

Deconvoluting post-transplant immunity: cell subset-specific mapping reveals pathways for activation and expansion of memory T, monocytes and B cells.

PubMed

Grigoryev, Yevgeniy A; Kurian, Sunil M; Avnur, Zafi; Borie, Dominic; Deng, Jun; Campbell, Daniel; Sung, Joanna; Nikolcheva, Tania; Quinn, Anthony; Schulman, Howard; Peng, Stanford L; Schaffer, Randolph; Fisher, Jonathan; Mondala, Tony; Head, Steven; Flechner, Stuart M; Kantor, Aaron B; Marsh, Christopher; Salomon, Daniel R

2010-10-14

A major challenge for the field of transplantation is the lack of understanding of genomic and molecular drivers of early post-transplant immunity. The early immune response creates a complex milieu that determines the course of ensuing immune events and the ultimate outcome of the transplant. The objective of the current study was to mechanistically deconvolute the early immune response by purifying and profiling the constituent cell subsets of the peripheral blood. We employed genome-wide profiling of whole blood and purified CD4, CD8, B cells and monocytes in tandem with high-throughput laser-scanning cytometry in 10 kidney transplants sampled serially pre-transplant, 1, 2, 4, 8 and 12 weeks. Cytometry confirmed early cell subset depletion by antibody induction and immunosuppression. Multiple markers revealed the activation and proliferative expansion of CD45RO(+)CD62L(-) effector memory CD4/CD8 T cells as well as progressive activation of monocytes and B cells. Next, we mechanistically deconvoluted early post-transplant immunity by serial monitoring of whole blood using DNA microarrays. Parallel analysis of cell subset-specific gene expression revealed a unique spectrum of time-dependent changes and functional pathways. Gene expression profiling results were validated with 157 different probesets matching all 65 antigens detected by cytometry. Thus, serial blood cell monitoring reflects the profound changes in blood cell composition and immune activation early post-transplant. Each cell subset reveals distinct pathways and functional programs. These changes illuminate a complex, early phase of immunity and inflammation that includes activation and proliferative expansion of the memory effector and regulatory cells that may determine the phenotype and outcome of the kidney transplant.

Absolute configuration of podophyllotoxone and its inhibitory activity against human prostate cancer cells.

PubMed

Li, Juan; Feng, Juan; Luo, Cheng; Herman, Ho-Yung Sung; Jiang, Ren-Wang

2015-01-01

Podophyllotoxone (1) was isolated from the roots of Dysosma versipellis. The structure was determined by spectroscopic analysis in combination with single-crystal X-ray analysis. The absolute configuration of compound 1 was assigned based on the Flack parameter. It showed significant inhibitory activities against human prostate cancer cells PC3 and DU145 with IC50 values being 14.7 and 20.6 μmol·L(-1), respectively. It also arrested the cells at G2/M phase. Tubulin polymerization assay showed that it inhibited the tubulin polymerization in a dose-dependent manner, and molecular docking analysis revealed a different binding mode with tubulin as compared with those known tubulin inhibitors. Copyright © 2015 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved.

Maternal Active Smoking During Pregnancy and Low Birth Weight in the Americas: A Systematic Review and Meta-analysis.

PubMed

Pereira, Priscilla Perez da Silva; Da Mata, Fabiana A F; Figueiredo, Ana Claudia Godoy; de Andrade, Keitty Regina Cordeiro; Pereira, Maurício Gomes

2017-05-01

Smoking during pregnancy may negatively impact newborn birth weight. This study investigates the relationship between maternal active smoking during pregnancy and low birth weight in the Americas through systematic review and meta-analysis. A literature search was conducted through indexed databases and the grey literature. Case-control and cohort studies published between 1984 and 2016 conducted within the Americas were included without restriction regarding publication language. The article selection process and data extraction were performed by two independent investigators. A meta-analysis of random effects was conducted, and possible causes of between-study heterogeneity were evaluated by meta-regressions and subgroup analyses. Publication bias was assessed by visual inspection of Begg's funnel plot and by Egger's regression test. The literature search yielded 848 articles from which 34 studies were selected for systematic review and 30 for meta-analysis. Active maternal smoking was associated with low birth weight, OR = 2.00 (95% CI: 1.77-2.26; I2 = 66.3%). The funnel plot and Egger's test (p = .14) indicated no publication bias. Meta-regression revealed that sample size, study quality, and the number of confounders in the original studies did not account for the between-study heterogeneity. Subgroup analysis indicated no significant differences when studies were compared by design, sample size, and regions of the Americas. Low birth weight is associated with maternal active smoking during pregnancy regardless of the region in the Americas or the studies' methodological aspects. A previous search of the major electronic databases revealed that no studies appear to have been conducted to summarize the association between maternal active smoking during pregnancy and low birth weight within the Americas. Therefore, this systematic review may help to fill the information gap. The region of the Americas contains some of the most populous countries in the world; therefore, this study may provide useful data from this massive segment of the world's population. © The Author 2017. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Purification and characterization of plantaricin Y, a novel bacteriocin produced by Lactobacillus plantarum 510.

PubMed

Chen, Yi-sheng; Wang, Yan-chong; Chow, Yiou-shing; Yanagida, Fujitoshi; Liao, Chen-chung; Chiu, Chi-ming

2014-03-01

Lactobacillus plantarum 510, previously isolated from a koshu vineyard in Japan, was found to produce a bacteriocin-like inhibitory substance which was purified and characterized. Mass spectrometry analysis showed that the mass of this bacteriocin is 4,296.65 Da. A partial sequence, NH2- SSSLLNTAWRKFG, was obtained by N-terminal amino acid sequence analysis. A BLAST search revealed that this is a unique sequence; this peptide is thus a novel bacteriocin produced by Lactobacillus plantarum 510 and was termed plantaricin Y. Plantaricin Y shows strong inhibitory activity against Listeria monocytogenes BCRC 14845, but no activity against other pathogens tested. Bacteriocin activity decreased slightly after autoclaving (121 °C for 15 min), but was completely inactivated by protease K. Furthermore, trypsin-digested bacteriocin product fragments retained activity against L. monocytogenes BCRC 14845 and exhibited a different inhibitory spectrum.

Preliminary efficacy of prize-based contingency management to increase activity levels in healthy adults.

PubMed

Washington, Wendy Donlin; Banna, Kelly M; Gibson, Amanda L

2014-01-01

An estimated 30% of Americans meet the criteria for obesity. Effective, low-cost interventions to increase physical activity are needed to prevent and treat obesity. In this study, 11 healthy adults wore Fitbit accelerometers for 3 weeks. During the initial baseline, subjects earned prize draws for wearing the Fitbit. During intervention, percentile schedules were used to calculate individual prize-draw criteria. The final week was a return to baseline. Four subjects increased step counts as a result of the intervention. A bout analysis of interresponse times revealed that subjects increased overall step counts by increasing daily minutes active and within-bout response rates and decreasing pauses between bouts of activity. Strategies to improve effectiveness are suggested, such as modification of reinforcement probability and amount and identification of the function of periods of inactivity. © Society for the Experimental Analysis of Behavior.

Cytotoxic and apoptosis-inducing activity of C21 steroids from the roots of Cynanchum atratum.

PubMed

Zhang, Jian; Ma, Lin; Wu, Zheng-Feng; Yu, Shu-Le; Wang, Lei; Ye, Wen-Cai; Zhang, Qing-Wen; Yin, Zhi-Qi

2017-06-01

Two new (1-2) and two known C 21 steroids (3-4) were isolated from the roots of Cynanchum atratum. Their structures were elucidated by detailed 1D and 2D spectroscopic. The MTT assay showed that compounds 1-4 displayed obvious cytotoxic activities against HepG2 cells with IC 50 values ranging from 10.19μM to 76.12μM. Compounds 1-3 also exhibited cytotoxic effects in A549 cells with IC 50 values of 30.87-95.39μM. Compound 3 showed the antiproliferative activity via G0/G1 cell cycle arrest and proapoptosis in HepG2 cells by Flowcytometry analysis. Western blotting analysis revealed that compound 3 could induce HepG2 cell apoptosis via the mitochondrial pathway by downregulating Bcl-2 expression, upregulating Bax protein expression, and activating caspase-9 and caspase-3. Copyright © 2017 Elsevier Inc. All rights reserved.

Soil enzymes as biodiagnostics indicator of heavy metal pollution of urbanozem

NASA Astrophysics Data System (ADS)

Novosyolova, E. I.; Volkova, O. O.; Turyanova, R. R.

2018-01-01

The article presents a comparative analysis of the impact of the introduction of different doses of copper and cadmium on the activity of redox enzymes of urbanozem, collected from different territories of Ufa. The studies established the inverse relationship of the activity of catalase and polyphenol oxidase, and the direct one of the activity of peroxidase that depends on the doses of heavy metals, that allows to recommend their use as bioindicator of pollution of urbanozem with these metals. The reaction of the studied enzymes on the introduction of heavy metals is an indicator of their toxicity to living things at the molecular level. Comparative analysis of the impact of cadmium and copper in different doses on the activity of soil enzymes did not reveal a uniform regularity. Each of the metals showed their toxicity in different ways depending on the duration of their impact.

Activation and manipulation of host responses by a Gram-positive bacterium

PubMed Central

Balaji, Vasudevan

2008-01-01

The interaction between tomato plants and Clavibacter michiganensis subsp. michiganensis (Cmm) represents a model pathosystem to study the interplay between the virulence determinants of a Gram-positive bacterium and the attempt of a crop plant to counteract pathogen invasion. To investigate plant responses activated during this compatible interaction, we recently analyzed gene expression profiles of tomato stems infected with Cmm. This analysis revealed activation of basal defense responses that are typically observed upon plant perception of pathogen-associated molecular patterns. In addition, Cmm infection upregulated the expression of host genes related to ethylene synthesis and response. Further analysis of tomato plants impaired in ethylene perception and production demonstrated an important role for ethylene in the development of disease symptoms. Here we discuss possible molecular strategies used by the plant to recognize Cmm infection and possible mechanisms employed by the pathogen to interfere with the activation of plant defense responses and promote disease. PMID:19704516

ENSO controls interannual fire activity in southeast Australia

NASA Astrophysics Data System (ADS)

Mariani, M.; Fletcher, M.-S.; Holz, A.; Nyman, P.

2016-10-01

El Niño-Southern Oscillation (ENSO) is the main mode controlling the variability in the ocean-atmosphere system in the South Pacific. While the ENSO influence on rainfall regimes in the South Pacific is well documented, its role in driving spatiotemporal trends in fire activity in this region has not been rigorously investigated. This is particularly the case for the highly flammable and densely populated southeast Australian sector, where ENSO is a major control over climatic variability. Here we conduct the first region-wide analysis of how ENSO controls fire activity in southeast Australia. We identify a significant relationship between ENSO and both fire frequency and area burnt. Critically, wavelet analyses reveal that despite substantial temporal variability in the ENSO system, ENSO exerts a persistent and significant influence on southeast Australian fire activity. Our analysis has direct application for developing robust predictive capacity for the increasingly important efforts at fire management.

AMP-regulated protein kinase activity in the hearts of mice treated with low- or high-fat diet measured using novel LC-MS method.

PubMed

Rybakowska, I M; Slominska, E M; Romaszko, P; Olkowicz, M; Kaletha, K; Smolenski, R T

2015-06-01

AMP-regulated protein kinase (AMPK) is involved in regulation of energy-generating pathways in response to the metabolic needs in different organs including the heart. The activity of AMPK is mainly controlled by AMP concentration that in turn could be affected by nucleotide metabolic pathways. This study aimed to develop a procedure for measurement of AMPK activity together with nucleotide metabolic enzymes and its application for studies of mice treated with high-fat diet. The method developed was based on analysis of conversion of AMARA peptide to pAMARA by partially purified heart homogenate by liquid chromatography/mass spectrometry (LC/MS). Activities of the enzymes of nucleotide metabolism were evaluated by analysis of conversion of substrates into products by HPLC. The method was applied for analysis of hearts of mice fed 12 weeks with low- (LFD) or high-fat diet (HFD). The optimized method for AMPK activity analysis (measured in presence of AMP) revealed change of activity from 0.089 ± 0.035 pmol/min/mg protein in LFD to 0.024 ± 0.002 in HFD. This coincided with increase of adenosine deaminase (ADA) activity from 0.11 ± 0.02 to 0.19 ± 0.06 nmol/mg tissue/min and decrease of AMP-deaminase (AMPD) activity from 1.26 ± 0.35 to 0.56 ± 0.15 nmol/mg tissue/min for LFD and HFD, respectively. We have proven quality of our LC/MS method for analysis of AMPK activity. We observed decrease in AMPK activity in the heart of mice treated with high-fat diet. However, physiological consequences of this change could be modulated by decrease in AMPD activity.

A PLC-γ1-independent, RasGRP1-ERK dependent pathway drives lymphoproliferative disease in LAT-Y136F mutant mice

PubMed Central

Kortum, Robert L.; Rouquette-Jazdanian, Alexandre K.; Miyaji, Michihiko; Merrill, Robert K.; Markegard, Evan; Pinski, John M.; Wesselink, Amelia; Nath, Nandan N.; Alexander, Clayton P.; Li, Wenmei; Kedei, Noemi; Roose, Jeroen P.; Blumberg, Peter M.; Samelson, Lawrence E.; Sommers, Connie L.

2012-01-01

Mice expressing a germline mutation in the PLC-γ1 binding site of LAT (linker for activation of T cells) show progressive lymphoproliferation and ultimately die at 4–6 months of age. The hyper-activated T cells in these mice show defective TCR-induced calcium flux, but enhanced Ras/ERK activation that is critical for disease progression. Despite the loss of LAT-dependent PLC-γ1 binding and activation, genetic analysis revealed RasGRP1, and not Sos1 or Sos2, to be the major RasGEF responsible for ERK activation and the lymphoproliferative phenotype in these mice. Analysis of isolated CD4+ T cells from LAT-Y136F mice showed altered proximal TCR-dependent kinase signaling, which activated a Zap70- and LAT-independent pathway. Moreover, LAT-Y136F T cells showed ERK activation that was dependent on Lck and/or Fyn, PKCθ, and RasGRP1. These data demonstrate a novel route to Ras activation in vivo in a pathological setting. PMID:23209318

Abnormal neural activities of directional brain networks in patients with long-term bilateral hearing loss.

PubMed

Xu, Long-Chun; Zhang, Gang; Zou, Yue; Zhang, Min-Feng; Zhang, Dong-Sheng; Ma, Hua; Zhao, Wen-Bo; Zhang, Guang-Yu

2017-10-13

The objective of the study is to provide some implications for rehabilitation of hearing impairment by investigating changes of neural activities of directional brain networks in patients with long-term bilateral hearing loss. Firstly, we implemented neuropsychological tests of 21 subjects (11 patients with long-term bilateral hearing loss, and 10 subjects with normal hearing), and these tests revealed significant differences between the deaf group and the controls. Then we constructed the individual specific virtual brain based on functional magnetic resonance data of participants by utilizing effective connectivity and multivariate regression methods. We exerted the stimulating signal to the primary auditory cortices of the virtual brain and observed the brain region activations. We found that patients with long-term bilateral hearing loss presented weaker brain region activations in the auditory and language networks, but enhanced neural activities in the default mode network as compared with normally hearing subjects. Especially, the right cerebral hemisphere presented more changes than the left. Additionally, weaker neural activities in the primary auditor cortices were also strongly associated with poorer cognitive performance. Finally, causal analysis revealed several interactional circuits among activated brain regions, and these interregional causal interactions implied that abnormal neural activities of the directional brain networks in the deaf patients impacted cognitive function.

Feminist music therapy pedagogy: a survey of music therapy educators.

PubMed

Hahna, Nicole D; Schwantes, Melody

2011-01-01

This study surveyed 188 music therapy educators regarding their views and use of feminist pedagogy and feminist music therapy. The purpose of this study was two-fold: (a) to determine how many music therapy educators used feminist pedagogy and (b) to determine if there was a relationship between the use of feminist pedagogy and academic rank of the participants. Seventy-two participants responded to this study, with 69 participants included for data analysis. Stake and Hoffman's (2000) feminist pedagogy survey was adapted for this study, examining four subscales of feminist pedagogy: (a) participatory learning, (b) validation of personal experience/development of confidence, (c) political/ social activism, and (d) critical thinking/open-mindedness. The results revealed that 46% (n=32) of participants identified as feminist music therapists and 67% (n=46) of participants identified as using feminist pedagogy. Results of a mixed analysis of variance revealed a statistically significant difference within the four survey subscales (p<.0001), no significant difference (p=.32) for academic rank, and no significant interaction (p=.08) of academic rank and the four survey subscales. Tukey's post hoc analysis of the data indicated that the survey subscale measuring political activism (p<.0001) was significantly lower than the other three survey subscales. In addition, a qualitative analysis on open-ended responses is also included. Discussion of the results, limitations, and areas for future research are addressed.

Risk assessment of Soulatrolide and Mammea (A/BA+A/BB) coumarins from Calophyllum brasiliense by a toxicogenomic and toxicological approach.

PubMed

Gomez-Verjan, J C; Estrella-Parra, E; Vazquez-Martinez, E R; Gonzalez-Sanchez, I; Guerrero-Magos, G; Mendoza-Villanueva, D; Isus, L; Alfaro, A; Cerbón-Cervantes, M; Aloy, P; Reyes-Chilpa, R

2016-05-01

Calophyllum brasiliense (Calophyllaceae) is a tropical rain forest tree distributed in Central and South America. It is an important source of tetracyclic dipyrano coumarins (Soulatrolide) and Mammea type coumarins. Soulatrolide is a potent inhibitor of HIV-1 reverse transcriptase and displays activity against Mycobacterium tuberculosis. Meanwhile, Mammea A/BA and A/BB, pure or as a mixture, are highly active against several human leukemia cell lines, Trypanosoma cruzi and Leishmania amazonensis. Nevertheless, there are few studies evaluating their safety profile. In the present work we performed toxicogenomic and toxicological analysis for both type of compounds. Soulatrolide, and the Mammea A/BA + A/BB mixture (2.1) were slightly toxic accordingly to Lorke assay classification (DL50 > 3000 mg/kg). After a short-term administration (100 mg/kg/daily, orally, 1 week) liver toxicogenomic analysis revealed 46 up and 72 downregulated genes for Mammea coumarins, and 665 up and 1077 downregulated genes for Soulatrolide. Gene enrichment analysis identified transcripts involved in drug metabolism for both compounds. In addition, network analysis through protein-protein interactions, tissue evaluation by TUNEL assay, and histological examination revealed no tissue damage on liver, kidney and spleen after treatments. Our results indicate that both type of coumarins displayed a safety profile, supporting their use in further preclinical studies to determine its therapeutic potential. Copyright © 2016 Elsevier Ltd. All rights reserved.

Proteome Analysis Using Isobaric Tags for Relative and Absolute Analysis Quantitation (iTRAQ) Reveals Alterations in Stress-Induced Dysfunctional Chicken Muscle.

PubMed

Xing, Tong; Wang, Chong; Zhao, Xue; Dai, Chen; Zhou, Guanghong; Xu, Xinglian

2017-04-05

The current study was designed to investigate changes in the protein profiles of pale, soft, and exudative (PSE)-like muscles of broilers subjected to transportation under high-temperature conditions, using isobaric tags for relative and absolute analysis quantitation (iTRAQ). Arbor Acres chickens (n = 112) were randomly divided into two treatments: unstressed control (CON) and 0.5 h of transport (T). Birds were transported according to a designed protocol. Pectoralis major (PM) muscle samples in the T group were collected and classified as normal (T-NOR) or PSE-like (T-PSE). Plasma activities of stress indicators, muscle microstructure, and proteome were measured. Results indicated that broilers in the T-PSE group exhibited higher activities of plasma stress indicators. The microstructure of T-PSE group showed a looser network and larger intercellular spaces in comparison to the other groups. Proteomic analysis, based on iTRAQ, revealed 29 differentially expressed proteins in the T-NOR and T-PSE groups that were involved in protein turnover, signal transduction, stress and defense, calcium handling, cell structure, and metabolism. In particular, proteins relating to the glycolysis pathway, calcium signaling, and molecular chaperones exhibited significant differences that may contribute to the inferior post-mortem meat quality. Overall, the proteomic results provide a further understanding of the mechanism of meat quality changes in response to stress.

Understanding the Acculturation Experience of Chinese Adolescent Students: Sociocultural Adaptation Strategies and a Positive Bicultural and Bilingual Identity

ERIC Educational Resources Information Center

Tong, Virginia M.

2014-01-01

The acculturation of Chinese immigrant high school students was examined as it relates to students' level of interaction with teachers and peers and participation in American school activities. Findings from a regression analysis revealed five variables (sociocultural adaptation strategies) that facilitate students' adjustment process:…

Proteomics analysis reveals protein expression differences for hypopharyngeal gland activity in the honeybee, Apis mellifera carnica Pollmann

USDA-ARS?s Scientific Manuscript database

Most of the proteins contained in royal jelly (RJ) are secreted from the hypopharyngeal glands (HG) of young bees. Although generic protein composition of RJ has been investigated, little is known about how age-dependent changes on HG secretion affect RJ composition and their biological consequences...

Relationship between Attributional Errors and At-Risk Behaviors among Juvenile Delinquents.

ERIC Educational Resources Information Center

Daley, Christine E.; Onwuegbuzie, Anthony J.

The purpose of this study was to determine whether at-risk behaviors (e.g., substance abuse, gun ownership, sexual activity, and gang membership) are associated with violence attribution errors, as measured by Daley and Onwuegbuzie's (1995) Violence Attribution Survey, among 82 incarcerated male juvenile delinquents. Analysis revealed that the…

A Quasi-Experimental Analysis of Schoolwide Violence Prevention Programs

ERIC Educational Resources Information Center

Barnes, Tia Navelene; Leite, Walter; Smith, Stephen W.

2017-01-01

Violence prevention programs are commonplace in today's schools, though reviews of the literature reveal mixed empirical findings on their effectiveness. Often, these programs include a variety of components such as social skills training, student mentoring, and activities designed to build a sense of school community that have not been tested for…

Analysis of Severe Injuries Associated with Volleyball Activities.

ERIC Educational Resources Information Center

Gerberich, Susan Goodwin; And Others

1987-01-01

Evaluation of 106 persons treated for injuries related to volleyball revealed that nearly 90 percent of injuries were concentrated in the lower extremities. Knee injuries accounted for 59 percent of injuries and ankle injuries accounted for about 23 percent of injuries. The mechanisms of jumping, landing, or twisting upon impact were highly…

Characteristics of Teacher Induction Programs and Turnover Rates of Beginning Teachers

ERIC Educational Resources Information Center

Kang, Seok; Berliner, David C.

2012-01-01

The federal School and Staffing Survey (SASS) and Teacher Follow-up Survey (TFS) were used to examine the impacts of induction activities on beginning teacher turnover. This study excluded those teachers who moved or left schools for unavoidable and involuntary reasons, a confounding factor in previous research. This analysis revealed that three…

Response of the small hive beetle (Aethina tumida) to a blend of chemicals identified from honeybee (Apis mellifera) volatiles

USDA-ARS?s Scientific Manuscript database

Coupled gas chromatographic-electroantennographic detection (GC-EAD) analyses of Super Q collected worker honey bee volatiles revealed several components that elicited antennal responses by the small hive beetle Aethina tumida. However, GC-MS analysis showed that eight of these EAD-active components...

Moving from Complaints to Action: Oppositional Consciousness and Collective Action in a Political Community

ERIC Educational Resources Information Center

Kwon, Soo Ah

2008-01-01

This article analyzes the process of youth political activism and development by drawing on ethnographic research on Asian and Pacific Islander youth activists. Young people revealed that collective action begins with a critical analysis of their lived experiences with inequalities. Their actions also involved oppositional consciousness that was…

A Comparative Analysis of Internal Communication and Public Relations Audits. State of the Art.

ERIC Educational Resources Information Center

Dozier, David M.; Hellweg, Susan A.

A review of current literature regarding the state of the art in the conduct of internal communication and public relations audits by public relations practitioners reveals that these two related measurement activities are of considerable importance to the practice of public relations. Public relations audits are concerned with exploratory…

Analysis of the Aspergillus flavus transcriptome reveals a key role of secondary metabolite production in isolate oxidative stress responses

USDA-ARS?s Scientific Manuscript database

The purpose of the production of secondary metabolites in fungi are various and include stress responses, competitive antimicrobial activity, and the elimination of toxic compounds. However, the purpose of the production of aflatoxin, a carcinogenic mycotoxin, by Aspergillus flavus, is unknown. Prev...

The Role of the Microcomputer-Based Laboratory Display in Supporting the Construction of New Understandings in Kinematics.

ERIC Educational Resources Information Center

Russell, David W.; Lucas, Keith B.; McRobbie, Campbell J.

2003-01-01

Investigates how microcomputer-based laboratory (MBL) activities specifically designed to be consistent with a constructivist theory of learning support or constrain student construction of understanding. Analysis of students' discourse and actions reveal that students invented numerous techniques for manipulating data in the service of their…

Style and Content in the Rhetoric of Early Afro-American Feminists.

ERIC Educational Resources Information Center

Campbell, Karlyn Kohrs

1986-01-01

Analyzes selected speeches by feminists active in the early Afro-American protest, revealing differences in their rhetoric and that of White feminists of the period. Argues that a simultaneous analysis and synthesis is necessary to understand these differences. Illustrates speeches by Sojourner Truth, Ida B. Wells, and Mary Church Terrell. (JD)

Components of Reflection: A Longitudinal Analysis of Study Abroad Student Blog Posts

ERIC Educational Resources Information Center

Savicki, Victor; Price, Michele V.

2017-01-01

Reflection supports actively transforming perspectives regarding study abroad experiences. The current study examines the "how" of reflection. Content of reflections is dictated by questions posed. The process of reflection is less prescribed yet revealing of paths to student understanding. Students posted to a web log (blog) over six…

Two proximal activating protein-1-binding sites are sufficient to stimulate transcription of the ovine follicle-stimulating hormone-beta gene

EPA Science Inventory

FSH is an important regulator of mammalian gametogenesis and the female reproductive cycle. Although little is known about the transcriptional regulation of the beta-subunit (the rate-limiting subunit of FSH synthesis), sequence analysis of the ovine FSHbeta promoter has revealed...

Transcriptional Network Analysis in Muscle Reveals AP-1 as a Partner of PGC-1α in the Regulation of the Hypoxic Gene Program

PubMed Central

Baresic, Mario; Salatino, Silvia; Kupr, Barbara

2014-01-01

Skeletal muscle tissue shows an extraordinary cellular plasticity, but the underlying molecular mechanisms are still poorly understood. Here, we use a combination of experimental and computational approaches to unravel the complex transcriptional network of muscle cell plasticity centered on the peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α), a regulatory nexus in endurance training adaptation. By integrating data on genome-wide binding of PGC-1α and gene expression upon PGC-1α overexpression with comprehensive computational prediction of transcription factor binding sites (TFBSs), we uncover a hitherto-underestimated number of transcription factor partners involved in mediating PGC-1α action. In particular, principal component analysis of TFBSs at PGC-1α binding regions predicts that, besides the well-known role of the estrogen-related receptor α (ERRα), the activator protein 1 complex (AP-1) plays a major role in regulating the PGC-1α-controlled gene program of the hypoxia response. Our findings thus reveal the complex transcriptional network of muscle cell plasticity controlled by PGC-1α. PMID:24912679

Sensitive luminescent reporter viruses reveal appreciable release of hepatitis C virus NS5A protein into the extracellular environment.

PubMed

Eyre, Nicholas S; Aloia, Amanda L; Joyce, Michael A; Chulanetra, Monrat; Tyrrell, D Lorne; Beard, Michael R

2017-07-01

The HCV NS5A protein is essential for viral RNA replication and virus particle assembly. To study the viral replication cycle and NS5A biology we generated an infectious HCV construct with a NanoLuciferase (NLuc) insertion within NS5A. Surprisingly, beyond its utility as a sensitive reporter of cytoplasmic viral RNA replication, we also observed strong luminescence in cell culture fluids. Further analysis using assembly-defective viruses and subgenomic replicons revealed that infectious virus production was not required for extracellular NS5A-NLuc activity but was associated with enrichment of extracellular NS5A-NLuc in intermediate-density fractions similar to those of exosomes and virus particles. Additionally, BRET analysis indicated that intracellular and extracellular forms of NS5A may adopt differing conformations. Importantly, infection studies using a human liver chimeric mouse model confirmed robust infection in vivo and ready detection of NLuc activity in serum. We hypothesise that the presence of NS5A in extracellular fluids contributes to HCV pathogenesis. Copyright © 2017 Elsevier Inc. All rights reserved.

Label-free quantitative proteomics reveals differentially regulated proteins in the latex of sticky diseased Carica papaya L. plants.

PubMed

Rodrigues, Silas P; Ventura, José A; Aguilar, Clemente; Nakayasu, Ernesto S; Choi, HyungWon; Sobreira, Tiago J P; Nohara, Lilian L; Wermelinger, Luciana S; Almeida, Igor C; Zingali, Russolina B; Fernandes, Patricia M B

2012-06-18

Papaya meleira virus (PMeV) is so far the only described laticifer-infecting virus, the causal agent of papaya (Carica papaya L.) sticky disease. The effects of PMeV on the laticifers' regulatory network were addressed here through the proteomic analysis of papaya latex. Using both 1-DE- and 1D-LC-ESI-MS/MS, 160 unique papaya latex proteins were identified, representing 122 new proteins in the latex of this plant. Quantitative analysis by normalized spectral counting revealed 10 down-regulated proteins in the latex of diseased plants, 9 cysteine proteases (chymopapain) and 1 latex serine proteinase inhibitor. A repression of papaya latex proteolytic activity during PMeV infection was hypothesized. This was further confirmed by enzymatic assays that showed a reduction of cysteine-protease-associated proteolytic activity in the diseased papaya latex. These findings are discussed in the context of plant responses against pathogens and may greatly contribute to understand the roles of laticifers in plant stress responses. Copyright © 2012 Elsevier B.V. All rights reserved.

In vitro and in vivo antibiofilm potential of 2,4-Di-tert-butylphenol from seaweed surface associated bacterium Bacillus subtilis against group A streptococcus.

PubMed

Viszwapriya, Dharmaprakash; Prithika, Udayakumar; Deebika, Sundaresan; Balamurugan, Krishnaswamy; Pandian, Shunmugiah Karutha

2016-10-01

Biofilm formation of Group A Streptococcus (GAS) is recognized as an important virulent determinant. The present study reports the antibiofilm potential of seaweed (Gracilaria gracilis) surface associated Bacillus subtilis against GAS. Purification revealed 2,4-Di-tert-butyl-phenol (DTBP) as the active principle. DTBP exhibited a dose dependent antibiofilm activity against GAS (SF370 & six different clinical M serotypes). Microscopic analysis revealed changes in cell surface architecture and reduced thickness upon DTBP treatment. Results of extracellular polymeric substance quantification, microbial adhesion to hydrocarbon assay and fourier transform infrared spectroscopic analysis suggested that DTBP probably interferes with the initial adhesion stage of biofilm formation cascade. Reduction in hyaluronic acid synthesis goes in unison with blood survival assay wherein, increased susceptibility to phagocytosis was observed. In vivo studies using Caenorhabditis elegans manifested the reduction in adherence and virulence, which prompts further investigation of the potential of DTBP for the treatment of GAS infections. Copyright © 2016 Elsevier GmbH. All rights reserved.

[Recurrence of chronic active Epstein-Barr virus infection presenting with myelopathy after umbilical cord blood transplantation].

PubMed

Watanabe, Shohei; Okada, Masaya; Tokugawa, Tazuko; Sawada, Akihiro; Ogawa, Hiroyasu; Yoshikawa, Hiroo

2014-01-01

A 38-year-old man was admitted to our hospital with neck pain, dysesthesia of both hands, and weakness of the left upper limb. He had been diagnosed with a chronic active Epstein-Barr virus infection (CAEBV) at the age of 34 and had undergone umbilical cord blood transplantation at the age of 37. MRI of the spinal cord revealed an intramedullary hyperintense lesion on T₂-weighted images with gadolinium enhancement. Because his laboratory tests revealed proliferation of CD19(+) lymphocytes in the peripheral blood, and EBV DNA was detected in both peripheral blood and CSF, he was diagnosed as having post-transplant EBV associated lymphoproliferative disease. However, chemotherapy did not alleviate his symptoms. At a later time, quantitative chimerism analysis of his CSF showed a higher proportion of lymphocytes that had originated from the recipient. Finally, he was diagnosed as having a recurrence of CAEBV in the central nervous system, and his symptoms were restored by intrathecal chemotherapy (methotrexate, cytosine arabinoside, and prednisolone). Quantitative chimerism analysis of CSF was useful for diagnosing the recurrence of CAEBV in the central nervous system.

Cloning and characterization of a Candida albicans maltase gene involved in sucrose utilization.

PubMed Central

Geber, A; Williamson, P R; Rex, J H; Sweeney, E C; Bennett, J E

1992-01-01

In order to isolate the structural gene involved in sucrose utilization, we screened a sucrose-induced Candida albicans cDNA library for clones expressing alpha-glucosidase activity. The C. albicans maltase structural gene (CAMAL2) was isolated. No other clones expressing alpha-glucosidase activity. were detected. A genomic CAMAL2 clone was obtained by screening a size-selected genomic library with the cDNA clone. DNA sequence analysis reveals that CAMAL2 encodes a 570-amino-acid protein which shares 50% identity with the maltase structural gene (MAL62) of Saccharomyces carlsbergensis. The substrate specificity of the recombinant protein purified from Escherichia coli identifies the enzyme as a maltase. Northern (RNA) analysis reveals that transcription of CAMAL2 is induced by maltose and sucrose and repressed by glucose. These results suggest that assimilation of sucrose in C. albicans relies on an inducible maltase enzyme. The family of genes controlling sucrose utilization in C. albicans shares similarities with the MAL gene family of Saccharomyces cerevisiae and provides a model system for studying gene regulation in this pathogenic yeast. Images PMID:1400249

Purification and partial characterization of a novel antibacterial agent (Bac1829) Produced by Staphylococcus aureus KSI1829.

PubMed Central

Crupper, S S; Iandolo, J J

1996-01-01

A novel antimicrobial agent from Staphylococcus aureus KSI1829, designated Bac1829, was purified by sequential steps of ammonium sulfate precipitation, Sephadex G-50 gel filtration chromatography, and hydrophobic interaction chromatography. Purified Bac1829 has a molecular mass of 6,418 +/- 2 Da. The peptide in heat stable, since full biological activity is retained after heating at 95 degrees C for 15 min, and it is destroyed by digestion with proteases. Amino acid sequence analysis revealed a high concentration of Ala and Gly residues, which respectively comprised 24 and 19% of the total amino acid content. Additionally, high levels of hydrophobic amino acids were present, accounting for the hydrophobic nature of Bac1829. Purified Bac1829 killed exponentially growing Corynebacterium renale in a dose-dependent manner by a bactericidal mode of action. A partial inhibitory spectrum analysis revealed that the following organisms were sensitive to the inhibitory activity of Bac1829: S. aureus RN4220, Streptococcus suis, Corynebacterium pseudotuberculosis, C. renale, Corynebacterium diptheriae, Haemophilus parasuis, Bordetella pertussis, Bordetella bronchoseptica, Moraxella bovis, and Pasteurella multocida. PMID:8795206

Identification of sequence motifs in oligonucleotides whose presence is correlated with antisense activity

PubMed Central

Matveeva, O. V.; Tsodikov, A. D.; Giddings, M.; Freier, S. M.; Wyatt, J. R.; Spiridonov, A. N.; Shabalina, S. A.; Gesteland, R. F.; Atkins, J. F.

2000-01-01

Design of antisense oligonucleotides targeting any mRNA can be much more efficient when several activity-enhancing motifs are included and activity-decreasing motifs are avoided. This conclusion was made after statistical analysis of data collected from >1000 experiments with phosphorothioate-modified oligonucleotides. Highly significant positive correlation between the presence of motifs CCAC, TCCC, ACTC, GCCA and CTCT in the oligonucleotide and its antisense efficiency was demonstrated. In addition, negative correlation was revealed for the motifs GGGG, ACTG, AAA and TAA. It was found that the likelihood of activity of an oligonucleotide against a desired mRNA target is sequence motif content dependent. PMID:10908347

Expression analysis of chitinase upon challenge inoculation to Alternaria wounding and defense inducers in Brassica juncea.

PubMed

Rawat, Sandhya; Ali, Sajad; Mittra, Bhabatosh; Grover, Anita

2017-03-01

Chitinases are the hydrolytic enzymes which belong to the pathogenesis-related (PR) protein family and play an important role not only in plant defense but also in various abiotic stresses. However, only a limited number of chitinase genes have been characterised in B. juncea . In this study, we have characterised B. juncea class IV chitinase gene (accession no EF586206) in response to fungal infection, salicylic acid (SA), jasmonic acid (JA) treatments and wounding. Gene expression studies revealed that the transcript levels of Bjchitinase ( BjChp ) gene increases significantly both in local and distal tissues after Alternaria infection. Bjchitinase gene was also induced by jasmonic acid and wounding but moderately by salicylic acid. A 2.5 kb class IV chitinase promoter of this gene was isolated from B. juncea by Genome walking (accession no KF055403.1). In-silico analysis of this promoter revealed a number of conserved cis -regulatory elements related to defense, wounding and signalling molecules like SA, and JA. For validation, chitinase promoter was fused to the GUS gene, and the resultant construct was then introduced into Arabidopsis plants. Histochemical analysis of T 2 transgenic Arabidopsis plants showed that higher GUS activity in leaves after fungal infection, wounding and JA treatment but weakly by SA. GUS activity was seen in meristematic tissues, young leaves, seeds and siliques. Finally investigation has led to the identification of a pathogen-inducible, developmentally regulated and organ-specific promoter. Present study revealed that Bjchitinase ( BjChp ) promoter is induced during biotic and environmental stress and it can be used in developing finely tuned transgenics.

Aspergillus Oryzae S2 α-Amylase Domain C Involvement in Activity and Specificity: In Vivo Proteolysis, Molecular and Docking Studies

PubMed Central

Sahnoun, Mouna; Jemli, Sonia; Trabelsi, Sahar; Ayadi, Leila; Bejar, Samir

2016-01-01

We previously reported that Aspergillus oryzae strain S2 had produced two α-amylase isoforms named AmyA and AmyB. The apparent molecular masses revealed by SDS-PAGE were 50 and 42 kDa, respectively. Yet AmyB has a higher catalytic efficiency. Based on a monitoring study of the α-amylase production in both the presence and absence of different protease inhibitors, a chymotrypsin proteolysis process was detected in vivo generating AmyB. A. oryzae S2 α-amylase gene was amplified, cloned and sequenced. The sequence analysis revealed nine exons, eight introns and an encoding open reading frame of 1500 bp corresponding to AmyA isoform. The amino-acid sequence analysis revealed aY371 potential chymotrypsin cleaving site, likely to be the AmyB C-Terminal end and two other potential sites at Y359, and F379. A zymogram with a high acrylamide concentration was used. It highlighted two other closed apparent molecular mass α-amylases termed AmyB1 and AmyB2 reaching40 kDa and 43 kDa. These isoforms could be possibly generated fromY359, and F379secondary cut, respectively. The molecular modeling study showed that AmyB preserved the (β/α)8 barrel domain and the domain B but lacked the C-terminal domain C. The contact map analysis and the docking studies strongly suggested a higher activity and substrate binding affinity for AmyB than AmyA which was previously experimentally exhibited. This could be explained by the easy catalytic cleft accessibility. PMID:27101008

Functional and phenotypical analysis of IL-6-secreting CD4+ T cells in human adipose tissue.

PubMed

de Jong, Anja J; Pollastro, Sabrina; Kwekkeboom, Joanneke C; Andersen, Stefan N; Dorjée, Annemarie L; Bakker, Aleida M; Alzaid, Fawaz; Soprani, Antoine; Nelissen, Rob G H H; Mullers, Jan B; Venteclef, Nicolas; de Vries, Niek; Kloppenburg, Margreet; Toes, René E M; Ioan-Facsinay, Andreea

2018-03-01

Emerging evidence indicates that a dynamic interplay between the immune system and adipocytes contributes to the disturbed homeostasis in adipose tissue of obese subjects. Recently, we observed IL-6-secretion by CD4 + T cells from the stromal vascular fraction (SVF) of the infrapatellar fat pad (IFP) of knee osteoarthritis patients directly ex vivo. Here we show that human IL-6 + CD4 + T cells from SVF display a more activated phenotype than the IL-6 - T cells, as evidenced by the expression of the activation marker CD69. Analysis of cytokines secretion, as well as expression of chemokine receptors and transcription factors associated with different Th subsets (Treg, Th1, Th2, Th17 and Tfh) revealed that IL-6-secreting CD4 + T cells cannot be assigned to a conventional Th subset. TCRβ gene analysis revealed that IL-6 + and IL-6 - CD4 + T cells appear clonally unrelated to each other, suggesting a different specificity of these cells. In line with these observations, adipocytes are capable of enhancing IL-6 production by CD4 + T cells. Thus, IL-6 + CD4 + T cells are TCRαβ T cells expressing an activated phenotype potentially resulting from an interplay with adipocytes that could be involved in the inflammatory processes in the OA joint. © 2017 The Authors. European Journal of Immunology published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Bioimpedance harmonic analysis as a tool to simultaneously assess circulation and nervous control.

PubMed

Mudraya, I S; Revenko, S V; Nesterov, A V; Gavrilov, I Yu; Kirpatovsky, V I

2011-07-01

Multicycle harmonic (Fourier) analysis of bioimpedance was employed to simultaneously assess circulation and neural activity in visceral (rat urinary bladder) and somatic (human finger) organs. The informative value of the first cardiac harmonic of the bladder impedance as an index of bladder circulation is demonstrated. The individual reactions of normal and obstructive bladders in response to infusion cystometry were recorded. The potency of multicycle harmonic analysis of bioimpedance to assess sympathetic and parasympathetic neural control in urinary bladder is discussed. In the human finger, bioimpedance harmonic analysis revealed three periodic components at the rate of the heart beat, respiration and Mayer wave (0.1 Hz), which were observed under normal conditions and during blood flow arrest in the hand. The revealed spectrum peaks were explained by the changes in systemic blood pressure and in regional vascular tone resulting from neural vasomotor control. During normal respiration and circulation, two side cardiac peaks were revealed in a bioimpedance amplitude spectrum, whose amplitude reflected the depth of amplitude respiratory modulation of the cardiac output. During normal breathing, the peaks corresponding to the second and third cardiac harmonics were split, reflecting frequency respiratory modulation of the heart rate. Multicycle harmonic analysis of bioimpedance is a novel potent tool to examine the interaction between the respiratory and cardiovascular system and to simultaneously assess regional circulation and neural influences in visceral and somatic organs.

Sex hormones adjust "sex-specific" reactive and diurnal cortisol profiles.

PubMed

Juster, Robert-Paul; Raymond, Catherine; Desrochers, Alexandra Bisson; Bourdon, Olivier; Durand, Nadia; Wan, Nathalie; Pruessner, Jens C; Lupien, Sonia J

2016-01-01

Sex differences in stress hormone functions are presumed to depend on sex hormones. And yet, surprisingly few psychoneuroendocrine studies actually assess within-sex variations of testosterone, estradiol, and progesterone when investigating sex-specific activities of the hypothalamic-pituitary-adrenal axis. In this methodological study of 204 healthy adults (60 men), we assessed whether cortisol profiles would differ between the sexes when unadjusted or adjusted for basal sex hormones among both sexes. Reactive cortisol was sampled using 6 saliva samples measured every 10-min as part of the Trier Social Stress Test that generally activates cortisol among men more than women. Diurnal cortisol was sampled over two days at (1) awakening, (2) 30-min thereafter, (3) 1400 h, (4) 1600 h, and (5) bedtime. Sex hormones were collected at baseline before the psychosocial stressor and on two occasions during diurnal cortisol assessment. Repeated-measures analysis of covariance controlled for key covariates in analyses unadjusted or adjusted for sex hormones. Results revealed that men had higher reactive cortisol than women in unadjusted analysis, but this sex difference was attenuated when adjusting for sex hormones. While diurnal cortisol showed no sex differences in unadjusted models, adjusting for sex hormones revealed that women have higher morning cortisol. Correlations using area under the curve formulae revealed intriguing sex-specific associations with progesterone in men and testosterone in women that we propose have implications for social and affective neuroscience. In summary, our results reveal that adjusting for sex hormones alters "sex-specific" reactive and diurnal cortisol profiles. Copyright © 2015 Elsevier Ltd. All rights reserved.

Structure and regulation of the Yersinia pestis yscBCDEF operon.

PubMed Central

Haddix, P L; Straley, S C

1992-01-01

We have investigated the physical and genetic structure and regulation of the Yersinia pestis yscBCDEF region, previously called lcrC. DNA sequence analysis showed that this region is homologous to the corresponding part of the ysc locus of Yersinia enterocolitica and suggested that the yscBCDEF cistrons belong to a single operon on the low-calcium response virulence plasmid pCD1. Promoter activity measurements of ysc subclones indicated that yscBCDEF constitutes a suboperon of the larger ysc region by revealing promoter activity in a clone containing the 3' end of yscD, intact yscE and yscF, and part of yscG. These experiments also revealed an additional weak promoter upstream of yscD. Northern (RNA) analysis with a yscD probe showed that operon transcription is thermally induced and downregulated in the presence of Ca2+. Primer extension of operon transcripts suggested that two promoters, a moderate-level constitutive one and a stronger, calcium-downregulated one, control full-length operon transcription at 37 degrees C. Primer extension provided additional support for the proposed designation of a yscBCDEF suboperon by identifying a 5' end within yscF, for which relative abundances in the presence and absence of Ca2+ revealed regulation that is distinct from that for transcripts initiating farther upstream. YscB and YscC were expressed in Escherichia coli by using a high-level transcription system. Attempts to express YscD were only partially successful, but they revealed interesting regulation at the translational level. Images PMID:1624469

Synthesis and Anti-cancer Activity of 3-substituted Benzoyl-4-substituted Phenyl-1H-pyrrole Derivatives.

PubMed

Zhan, Xiaoping; Qin, Weixi; Wang, Shuai; Zhao, Kai; Xin, Yuxuan; Wang, Yaolin; Qi, Qi; Mao, Zhenmin

2017-01-01

Cancer is considered a major public health problem worldwide. The aim of this paper is to design and synthesis of novel anticancer agents with potent anticancer activity and minimum side effects. A series of pyrrole derivatives were synthesized, their anti-cancer activity against nine cancer cell lines and two non-cancer cell lines were evaluated by MTT assay, and their cell cycle progression were determined by flow cytometry analysis. The study of the structure-activity relationships revealed that the introduction of the electron-donation groups at the 4th position of the pyrrole ring increased the anti-cancer activity. Among the synthesized compounds, specially the compounds bearing 3,4-dimethoxy phenyl at the 4th position of the pyrrole ring showed potent anti-cancer activity, cpd 19 was the most potent against MGC 80-3, HCT-116 and CHO cell lines (IC50s = 1.0－1.7 μM), cpd 21 was the most potent against HepG2, DU145 and CT-26 cell lines (IC50s = 0.5－0.9 μM), and cpd 15 was the most potent against A549 (IC50 = 3.6 μM). Moreover, these potent compounds showed weak cytotoxicity against HUVEC and NIH/3T3. Thus, the cpds 15, 19 and 21 show potential anti-cancer for further investigation. Furthermore, the flow cytometry analysis revealed that cpd 21 arrested the CT-26 cells at S phase, and induced the cell apoptosis. Thus, these compounds with the potent anticancer activity and low toxicity have potential for the development of new anticancer chemotherapy agents. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

The Structural Basis for Activation and Inhibition of ZAP-70 Kinase Domain.

PubMed

Huber, Roland G; Fan, Hao; Bond, Peter J

2015-10-01

ZAP-70 (Zeta-chain-associated protein kinase 70) is a tyrosine kinase that interacts directly with the activated T-cell receptor to transduce downstream signals, and is hence a major player in the regulation of the adaptive immune response. Dysfunction of ZAP-70 causes selective T cell deficiency that in turn results in persistent infections. ZAP-70 is activated by a variety of signals including phosphorylation of the kinase domain (KD), and binding of its regulatory tandem Src homology 2 (SH2) domains to the T cell receptor. The present study investigates molecular mechanisms of activation and inhibition of ZAP-70 via atomically detailed molecular dynamics simulation approaches. We report microsecond timescale simulations of five distinct states of the ZAP-70 KD, comprising apo, inhibited and three phosphorylated variants. Extensive analysis of local flexibility and correlated motions reveal crucial transitions between the states, thus elucidating crucial steps in the activation mechanism of the ZAP-70 KD. Furthermore, we rationalize previously observed staurosporine-bound crystal structures, suggesting that whilst the KD superficially resembles an "active-like" conformation, the inhibitor modulates the underlying protein dynamics and restricts it in a compact, rigid state inaccessible to ligands or cofactors. Finally, our analysis reveals a novel, potentially druggable pocket in close proximity to the activation loop of the kinase, and we subsequently use its structure in fragment-based virtual screening to develop a pharmacophore model. The pocket is distinct from classical type I or type II kinase pockets, and its discovery offers promise in future design of specific kinase inhibitors, whilst mutations in residues associated with this pocket are implicated in immunodeficiency in humans.

The Structural Basis for Activation and Inhibition of ZAP-70 Kinase Domain

PubMed Central

Huber, Roland G.; Fan, Hao; Bond, Peter J.

2015-01-01

ZAP–70 (Zeta-chain-associated protein kinase 70) is a tyrosine kinase that interacts directly with the activated T-cell receptor to transduce downstream signals, and is hence a major player in the regulation of the adaptive immune response. Dysfunction of ZAP–70 causes selective T cell deficiency that in turn results in persistent infections. ZAP–70 is activated by a variety of signals including phosphorylation of the kinase domain (KD), and binding of its regulatory tandem Src homology 2 (SH2) domains to the T cell receptor. The present study investigates molecular mechanisms of activation and inhibition of ZAP–70 via atomically detailed molecular dynamics simulation approaches. We report microsecond timescale simulations of five distinct states of the ZAP–70 KD, comprising apo, inhibited and three phosphorylated variants. Extensive analysis of local flexibility and correlated motions reveal crucial transitions between the states, thus elucidating crucial steps in the activation mechanism of the ZAP–70 KD. Furthermore, we rationalize previously observed staurosporine-bound crystal structures, suggesting that whilst the KD superficially resembles an “active-like” conformation, the inhibitor modulates the underlying protein dynamics and restricts it in a compact, rigid state inaccessible to ligands or cofactors. Finally, our analysis reveals a novel, potentially druggable pocket in close proximity to the activation loop of the kinase, and we subsequently use its structure in fragment-based virtual screening to develop a pharmacophore model. The pocket is distinct from classical type I or type II kinase pockets, and its discovery offers promise in future design of specific kinase inhibitors, whilst mutations in residues associated with this pocket are implicated in immunodeficiency in humans. PMID:26473606

Screening molecular associations with lipid membranes using natural abundance 13C cross-polarization magic-angle spinning NMR and principal component analysis.

PubMed

Middleton, David A; Hughes, Eleri; Madine, Jillian

2004-08-11

We describe an NMR approach for detecting the interactions between phospholipid membranes and proteins, peptides, or small molecules. First, 1H-13C dipolar coupling profiles are obtained from hydrated lipid samples at natural isotope abundance using cross-polarization magic-angle spinning NMR methods. Principal component analysis of dipolar coupling profiles for synthetic lipid membranes in the presence of a range of biologically active additives reveals clusters that relate to different modes of interaction of the additives with the lipid bilayer. Finally, by representing profiles from multiple samples in the form of contour plots, it is possible to reveal statistically significant changes in dipolar couplings, which reflect perturbations in the lipid molecules at the membrane surface or within the hydrophobic interior.

Observation of Bernstein Waves Excited by Newborn Interstellar Pickup Ions in the Solar Wind

NASA Technical Reports Server (NTRS)

Joyce, Colin J.; Smith, Charles W.; Isenberg, Philip A.; Gary, S. Peter; Murphy, Neil; Gray, Perry C.; Burlaga, Leonard F.

2012-01-01

A recent examination of 1.9 s magnetic field data recorded by the Voyager 2 spacecraft in transit to Jupiter revealed several instances of strongly aliased spectra suggestive of unresolved high-frequency magnetic fluctuations at 4.4 AU. A closer examination of these intervals using the highest resolution data available revealed one clear instance of wave activity at spacecraft frame frequencies from 0.2 to 1 Hz. Using various analysis techniques, we have characterized these fluctuations as Bernstein mode waves excited by newborn interstellar pickup ions. We can find no other interpretation or source consistent with the observations, but this interpretation is not without questions. In this paper, we report a detailed analysis of the waves, including their frequency and polarization, that supports our interpretation.

A missense mutation in the human cytochrome b5 gene causes 46,XY disorder of sex development due to true isolated 17,20 lyase deficiency.

PubMed

Idkowiak, Jan; Randell, Tabitha; Dhir, Vivek; Patel, Pushpa; Shackleton, Cedric H L; Taylor, Norman F; Krone, Nils; Arlt, Wiebke

2012-03-01

Isolated 17,20 lyase deficiency is commonly defined by apparently normal 17α-hydroxylase activity but severely reduced 17,20 lyase activity of the bifunctional enzyme cytochrome P450 (CYP) enzyme 17A1 (CYP17A1), resulting in sex steroid deficiency but normal glucocorticoid and mineralocorticoid reserve. Cytochrome b5 (CYB5A) is thought to selectively enhance 17,20 lyase activity by facilitating the allosteric interaction of CYP17A1 with its electron donor P450 oxidoreductase (POR). We investigated a large consanguineous family including three siblings with 46,XY disorder of sex development (DSD) presenting with isolated 17,20 lyase deficiency. We investigated the clinical and biochemical phenotype, conducted genetic analyses, and functionally characterized the identified CYB5A mutation in cell-based CYP17A1 coexpression assays. All three siblings presented with 46,XY DSD, sex steroid deficiency, normal mineralocorticoids and glucocorticoids, and a urine steroid metabolome suggestive of isolated 17,20 lyase deficiency. CYP17A1 and POR sequences were normal, but we detected a homozygous CYB5A missense mutation (g.28,400A→T; p.H44L). Functional in vitro analysis revealed normal CYP17A1 17α-hydroxylase activity but severely impaired 17,20 lyase activity. In silico analysis suggested the disruption of CYB5A heme binding by p.H44L. We have identified the first human CYB5A missense mutation as the cause of isolated 17,20 lyase deficiency in three individuals with 46,XY DSD. Detailed review of previously reported cases with apparently isolated 17,20 lyase deficiency due to mutant CYP17A1 and POR reveals impaired 17α-hydroxylase activity as assessed by steroid metabolome analysis and short cosyntropin testing. This suggests that truly isolated 17,20 lyase deficiency is observed only in individuals with inactivating CYB5A mutations.

Cholinesterase inhibitory, anti-amyloidogenic and neuroprotective effect of the medicinal plant Grewia tiliaefolia - An in vitro and in silico study.

PubMed

Sheeja Malar, Dicson; Beema Shafreen, Rajamohamed; Karutha Pandian, Shunmugiah; Pandima Devi, Kasi

2017-12-01

Grewia tiliaefolia Vahl. (Tiliaceae) is a sub-tropical plant used as an indigenous medicine in India. However, its efficacy has not been evaluated against Alzheimer's disease. The objective of this study is to evaluate cholinesterase inhibitory, anti-aggregation and neuroprotective activity of G. tiliaefolia. Grewia tiliaefolia leaves were collected from Eastern Ghats region, India, and subjected to successive extraction (petroleum ether, chloroform, ethyl acetate, methanol and water). The extracts were subjected to in vitro antioxidant, anticholinesterase and anti-aggregation assays. The active methanol extract (MEGT) was separated using column chromatography. LC-MS analysis was done and the obtained compounds were docked against acetylcholinesterase (AChE) enzyme to identify the active component. Antioxidant assays demonstrated that the MEGT showed significant free radical scavenging activity at the IC 50 value of 71.5 ± 1.12 μg/mL. MEGT also exhibited significant dual cholinesterase inhibition with IC 50 value of 64.26 ± 2.56 and 54 ± 0.7 μg/mL for acetyl and butyrylcholinesterase (BChE), respectively. Also, MEGT showed significant anti-aggregation activity by preventing the oligomerization of Aβ 25-35 . Further, MEGT increased the viability of Neuro2a cells up to 95% against Aβ 25-35 neurotoxicity. LC-MS analysis revealed the presence of 16 compounds including vitexin, ellagic acid, isovitexin, etc. In silico analysis revealed that vitexin binds effectively with AChE through strong hydrogen bonding. These results were further confirmed by evaluating the activity of vitexin in vitro, which showed dual cholinesterase inhibition with IC 50 value of 15.21 ± 0.41 and 19.75 ± 0.16 μM for acetyl and butyrlcholinesterase, respectively. Grewia tiliaefolia can be considered as a promising therapeutic agent for the treatment of AD.

The fabrication of porous N-doped carbon from widely available urea formaldehyde resin for carbon dioxide adsorption.

PubMed

Liu, Zhen; Du, Zhenyu; Song, Hao; Wang, Chuangye; Subhan, Fazle; Xing, Wei; Yan, Zifeng

2014-02-15

N-doped carbon material constitutes abundant of micropores and basic nitrogen species that have potential implementation for CO2 capture. In this paper, porous carbon material with high nitrogen content was simply fabricated by carbonizing low cost and widely available urea formaldehyde resin, and then followed by KOH activation. CO2 capture experiment showed high adsorption capacity of 3.21 mmol g(-1) at 25 °C under 1 atm for UFCA-2-600. XRD, SEM, XPS and FT-IR analysis confirmed that a graphitic-like structure was retained even after high temperature carbonization and strong base activation. Textural property analysis revealed that narrow micropores, especially below 0.8 nm, were effective for CO2 adsorption by physical adsorption mechanism. Chemical evolved investigation revealed that graphitic-like embedded basic nitrogen groups are generated from bridged and terminal amines of urea formaldehyde resin from thermal carbonization and KOH activation treatment, which is responsible for the enrichment of CO2 capacity by chemical adsorption mechanism. The relationship between CO2 adsorption capacity and pore size or basic N species was also studied, which turned out that both of them played crucial role by physical and chemical adsorption mechanism, respectively. Copyright © 2013 Elsevier Inc. All rights reserved.

Phylogenetic appearance of Neuropeptide S precursor proteins in tetrapods

PubMed Central

Reinscheid, Rainer K.

2007-01-01

Sleep and emotional behavior are two hallmarks of vertebrate animal behavior, implying that specialized neuronal circuits and dedicated neurochemical messengers may have been developed during evolution to regulate such complex behaviors. Neuropeptide S (NPS) is a newly identified peptide transmitter that activates a typical G protein-coupled receptor. Central administration of NPS produces profound arousal, enhances wakefulness and suppresses all stages of sleep. In addition, NPS can alleviate behavioral responses to stress by producing anxiolytic-like effects. A bioinformatic analysis of current genome databases revealed that the NPS peptide precursor gene is present in all vertebrates with the exception of fish. A high level of sequence conservation, especially of aminoterminal structures was detected, indicating stringent requirements for agonist-induced receptor activation. Duplication of the NPS precursor gene was only found in one out of two marsupial species with sufficient genome coverage (Monodelphis domestica; opossum), indicating that the duplicated opossum NPS sequence might have arisen as an isolated event. Pharmacological analysis of both Monodelphis NPS peptides revealed that only the closely related NPS peptide retained agonistic activity at NPS receptors. The duplicated precursor might be either a pseudogene or could have evolved different receptor selectivity. Together, these data show that NPS is a relatively recent gene in vertebrate evolution whose appearance might coincide with its specialized physiological functions in terrestrial vertebrates. PMID:17293003

Wide-scale quantitative phosphoproteomic analysis reveals that cold treatment of T cells closely mimics soluble antibody stimulation

PubMed Central

Ji, Qinqin; Salomon, Arthur R.

2015-01-01

The activation of T-lymphocytes through antigen-mediated T-cell receptor (TCR) clustering is vital in regulating the adaptive-immune response. Although T cell receptor signaling has been extensively studied, the fundamental mechanisms for signal initiation are not fully understood. Reduced temperature initiated some of the hallmarks of TCR signaling such as increased phosphorylation and activation on ERK and calcium release from the endoplasmic reticulum as well as coalesce T-cell membrane microdomains. The precise mechanism of TCR signaling initiation due to temperature change remains obscure. One critical question is whether signaling initiated by cold treatment of T cells differs from signaling initiated by crosslinking of the T cell receptor. To address this uncertainty, a wide-scale, quantitative mass spectrometry-based phosphoproteomic analysis was performed on T cells stimulated either by temperature shift or through crosslinking of the TCR. Careful statistical comparison between the two stimulations revealed a striking level of identity between the subset of 339 sites that changed significantly with both stimulations. This study demonstrates for the first time, at unprecedented detail, that T cell cold treatment was sufficient to initiate signaling patterns nearly identical to soluble antibody stimulation, shedding new light on the mechanism of activation of these critically important immune cells. PMID:25839225

Repression of enhancer II activity by a negative regulatory element in the hepatitis B virus genome.

PubMed Central

Lo, W Y; Ting, L P

1994-01-01

Enhancer II of human hepatitis B virus has dual functions in vivo. Located at nucleotides (nt) 1646 to 1741, it can stimulate the surface and X promoters from a downstream position. Moreover, the same sequence can also function as upstream regulatory element that activates the core promoter in a position- and orientation-dependent manner. In this study, we report the identification and characterization of a negative regulatory element (NRE) upstream of enhancer II (nt 1613 to 1636) which can repress both the enhancer and upstream stimulatory function of the enhancer II sequence in differentiated liver cells. This NRE has marginal inhibitory effect by itself but a strong repressive function in the presence of a functional enhancer II. Mutational analysis reveals that sequence from nt 1616 to 1621 is required for repression of enhancer activity by the NRE. Gel shift analysis reveals that this negative regulatory region can be recognized by a specific protein factor(s) present at the 0.4 M NaCl fraction of HepG2 nuclear extracts. The discovery of the NRE indicates that HBV gene transcription is controlled by combined effects of both positive and negative regulation. It also provides a unique system with which to study the mechanism of negative regulation of gene expression. Images PMID:8107237

The synthesis of Ba2+ doped multiferroic BiFeO3 nanoparticles by using a hydrothermal approach in the presence of different surface activators and the investigation of structural and magnetic features

NASA Astrophysics Data System (ADS)

Mardani, Reza

2017-05-01

In this work, Bi1-x Ba x FeO3 nanoparticles were synthesized by a hydrothermal method in the presence of various surface activators, and different amounts of barium were inserted in a bismuth ferrite (x  =  0.1, 0.15, 0.2) structure instead of bismuth. The structural and magnetic properties, morphology, and size of the synthesized nanoparticles were investigated by XRD, FT-IR, FE-SEM, TEM, DLS and VSM. The XRD analysis results reveal that the synthetic nanoparticles have a single phase. A phase shift from a rhombohedral structure to a tetragonal structure occurs due to the enhanced barium amount in the bismuth ferrite structure. The SEM analysis exhibits a uniform shape of the Bi0.85Ba0.15FeO3 particles and the image observed by TEM clarifies the size of the particles as 11 nm. Furthermore, the effect of the diverse surfaces of activators in the synthesis of Bi0.85Ba0.15FeO3 nanoparticles was studied, revealing that when sugar was used as a surfactant, the particle size reduced and the magnetic properties increased notably.

Cognitive inhibition of number/length interference in a Piaget-like task: evidence by combining ERP and MEG.

PubMed

Joliot, Marc; Leroux, Gaëlle; Dubal, Stéphanie; Tzourio-Mazoyer, Nathalie; Houdé, Olivier; Mazoyer, Bernard; Petit, Laurent

2009-08-01

We combined event-related potential (ERP) and magnetoencephalography (MEG) acquisition and analysis to investigate the electrophysiological markers of the inhibitory processes involved in the number/length interference in a Piaget-like numerical task. Eleven healthy subjects performed four gradually interfering conditions with the heuristic "length equals number" to be inhibited. Low resolution tomography reconstruction was performed on the combined grand averaged electromagnetic data at the early (N1, P1) and late (P2, N2, P3(early) and P3(late)) latencies. Every condition was analyzed at both scalp and regional brain levels. The inhibitory processes were visible on the late components of the electromagnetic brain activity. A right P2-related frontal orbital activation reflected the change of strategy in the inhibitory processes. N2-related SMA/cingulate activation revealed the first occurrence of the stimuli processing to be inhibited. Both P3 components revealed the working memory processes operating in a medial temporal complex and the mental imagery processes subtended by the precuneus. Simultaneous ERP and MEG signal acquisition and analysis allowed to describe the spatiotemporal patterns of neural networks involved in the inhibition of the "length equals number" interference. Combining ERP and MEG ensured a sensitivity which could be reached previously only through invasive intracortical recordings.

Spatio-temporal source cluster analysis reveals fronto-temporal auditory change processing differences within a shared autistic and schizotypal trait phenotype.

PubMed

Ford, Talitha C; Woods, Will; Crewther, David P

2017-01-01

Social Disorganisation (SD) is a shared autistic and schizotypal phenotype that is present in the subclinical population. Auditory processing deficits, particularly in mismatch negativity/field (MMN/F) have been reported across both spectrum disorders. This study investigates differences in MMN/F cortical spatio-temporal source activity between higher and lower quintiles of the SD spectrum. Sixteen low (9 female) and 19 high (9 female) SD subclinical adults (18-40years) underwent magnetoencephalography (MEG) during an MMF paradigm where standard tones (50ms) were interrupted by infrequent duration deviants (100ms). Spatio-temporal source cluster analysis with permutation testing revealed no difference between the groups in source activation to the standard tone. To the deviant tone however, there was significantly reduced right hemisphere fronto-temporal and insular cortex activation for the high SD group ( p = 0.038). The MMF, as a product of the cortical response to the deviant minus that to the standard, did not differ significantly between the high and low Social Disorganisation groups. These data demonstrate a deficit in right fronto-temporal processing of an auditory change for those with more of the shared SD phenotype, indicating that right fronto-temporal auditory processing may be associated with psychosocial functioning.

Secretomic survey of Trichoderma harzianum grown on plant biomass substrates.

PubMed

Gómez-Mendoza, Diana Paola; Junqueira, Magno; do Vale, Luis Henrique Ferreira; Domont, Gilberto Barbosa; Ferreira Filho, Edivaldo Ximenes; Sousa, Marcelo Valle de; Ricart, Carlos André Ornelas

2014-04-04

The present work aims at characterizing T. harzianum secretome when the fungus is grown in synthetic medium supplemented with one of the four substrates: glucose, cellulose, xylan, and sugarcane bagasse (SB). The characterization was done by enzymatic assays and proteomic analysis using 2-DE/MALDI-TOF and gel-free shotgun LC-MS/MS. The results showed that SB induced the highest cellulolytic and xylanolytic activities when compared with the other substrates, while remarkable differences in terms of number and distribution of protein spots in 2-DE gels were also observed among the samples. Additionally, treatment of the secretomes with PNGase F revealed that most spot trails in 2-DE gels corresponded to N-glycosylated proteoforms. The LC-MS/MS analysis of the samples identified 626 different protein groups, including carbohydrate-active enzymes and accessory, noncatalytic, and cell-wall-associated proteins. Although the SB-induced secretome displayed the highest cellulolytic and xylanolytic activities, it did not correspond to a higher proteome complexity because CM-cellulose-induced secretome was significantly more diverse. Among the identified proteins, 73% were exclusive to one condition, while only 5% were present in all samples. Therefore, this study disclosed the variation of T. harzianum secretome in response to different substrates and revealed the diversity of the fungus enzymatic toolbox.

Anthelmintic activity of trans-cinnamaldehyde and A- and B-type proanthocyanidins derived from cinnamon (Cinnamomum verum)

PubMed Central

Williams, Andrew R.; Ramsay, Aina; Hansen, Tina V. A.; Ropiak, Honorata M.; Mejer, Helena; Nejsum, Peter; Mueller-Harvey, Irene; Thamsborg, Stig M.

2015-01-01

Cinnamon (Cinnamomum verum) has been shown to have anti-inflammatory and antimicrobial properties, but effects on parasitic worms of the intestine have not been investigated. Here, extracts of cinnamon bark were shown to have potent in vitro anthelmintic properties against the swine nematode Ascaris suum. Analysis of the extract revealed high concentrations of proanthocyanidins (PAC) and trans-cinnamaldehyde (CA). The PAC were subjected to thiolysis and HPLC-MS analysis which demonstrated that they were exclusively procyanidins, had a mean degree of polymerization of 5.2 and 21% of their inter-flavan-3-ol links were A-type linkages. Purification of the PAC revealed that whilst they had activity against A. suum, most of the potency of the extract derived from CA. Trichuris suis and Oesophagostomum dentatum larvae were similarly susceptible to CA. To test whether CA could reduce A. suum infection in pigs in vivo, CA was administered daily in the diet or as a targeted, encapsulated dose. However, infection was not significantly reduced. It is proposed that the rapid absorption or metabolism of CA in vivo may prevent it from being present in sufficient concentrations in situ to exert efficacy. Therefore, further work should focus on whether formulation of CA can enhance its activity against internal parasites. PMID:26420588

New Frontiers and Challenges for Single-Cell Electrochemical Analysis.

PubMed

Zhang, Jingjing; Zhou, Junyu; Pan, Rongrong; Jiang, Dechen; Burgess, James D; Chen, Hong-Yuan

2018-02-23

Previous measurements of cell populations might obscure many important cellular differences, and new strategies for single-cell analyses are urgently needed to re-examine these fundamental biological principles for better diagnosis and treatment of diseases. Electrochemistry is a robust technique for the analysis of single living cells that has the advantages of minor interruption of cellular activity and provides the capability of high spatiotemporal resolution. The achievements of the past 30 years have revealed significant information about the exocytotic events of single cells to elucidate the mechanisms of cellular activity. Currently, the rapid developments of micro/nanofabrication and optoelectronic technologies drive the development of multifunctional electrodes and novel electrochemical approaches with higher resolution for single cells. In this Perspective, three new frontiers in this field, namely, electrochemical microscopy, intracellular analysis, and single-cell analysis in a biological system (i.e., neocortex and retina), are reviewed. The unique features and remaining challenges of these techniques are discussed.

Fathers’ perspectives on the diets and physical activity behaviours of their young children

PubMed Central

Hesketh, Kylie D.; van der Pligt, Paige; Cameron, Adrian J.; Crawford, David; Campbell, Karen J.

2017-01-01

Background Children’s learning about food and physical activity is considerable during their formative years, with parental influence pivotal. Research has focused predominantly on maternal influences with little known about the relationships between fathers’ and young children’s dietary and physical activity behaviours. A greater understanding of paternal beliefs regarding young children’s dietary and physical activity behaviours is important to inform the design and delivery of child-focussed health promotion interventions. This study aimed to describe fathers’ perceived roles in their children’s eating and physical activity behaviours. It also sought to document fathers’ views regarding how they could be best supported to promote healthy eating and physical activity behaviours in their young children. Methods In depth, semi-structured interviews were conducted with twenty fathers living in socio-economically diverse areas of metropolitan Melbourne, Australia who had at least one child aged five years or less. All interviews were audio recorded, transcribed verbatim and thematically analysed. Results Thematic analysis of the transcripts revealed eight broad themes about fathers’ beliefs, perceptions and attitudes towards the dietary and physical activity behaviours of their young children: (i) shared responsibility and consultation; (ii) family meal environment; (iii) parental role modelling; (iv) parental concerns around food; (v) food rewards; (vi) health education; (vii) limiting screen time; and (viii) parental knowledge. Analysis of themes according to paternal education/employment revealed no substantial differences in the views of fathers. Conclusions This exploratory study presents the views of a socio-economically diverse group of fathers regarding the dietary and physical activity behaviours of their young children and the insights into the underlying perceptions informing these views. The findings suggest that fathers believe healthy eating behaviours and being physically active are important for their young children. Fathers believe these behaviours can be promoted and supported in different ways including through the provision of appropriate meal and physical activity environments and parental role modelling of desired dietary and physical activity behaviours. PMID:28604810

Distinct summer and winter bacterial communities in the active layer of Svalbard permafrost revealed by DNA- and RNA-based analyses

DOE PAGES

Schostag, Morten; Stibal, Marek; Jacobsen, Carsten S.; ...

2015-04-30

The active layer of soil overlaying permafrost in the Arctic is subjected to dramatic annual changes in temperature and soil chemistry, which likely affect bacterial activity and community structure. We studied seasonal variations in the bacterial community of active layer soil from Svalbard (78°N) by co-extracting DNA and RNA from 12 soil cores collected monthly over a year. PCR amplicons of 16S rRNA genes (DNA) and reverse transcribed transcripts (cDNA) were quantified and sequenced to test for the effect of low winter temperature and seasonal variation in concentration of easily degradable organic matter on the bacterial communities. The copy numbermore » of 16S rRNA genes and transcripts revealed no distinct seasonal changes indicating potential bacterial activity during winter despite soil temperatures well below -10°C. Multivariate statistical analysis of the bacterial diversity data (DNA and cDNA libraries) revealed a season-based clustering of the samples, and, e.g., the relative abundance of potentially active Cyanobacteria peaked in June and Alphaproteobacteria increased over the summer and then declined from October to November. The structure of the bulk (DNA-based) community was significantly correlated with pH and dissolved organic carbon, while the potentially active (RNA-based) community structure was not significantly correlated with any of the measured soil parameters. A large fraction of the 16S rRNA transcripts was assigned to nitrogen-fixing bacteria (up to 24% in June) and phototrophic organisms (up to 48% in June) illustrating the potential importance of nitrogen fixation in otherwise nitrogen poor Arctic ecosystems and of phototrophic bacterial activity on the soil surface.« less

Distinct summer and winter bacterial communities in the active layer of Svalbard permafrost revealed by DNA- and RNA-based analyses

PubMed Central

Schostag, Morten; Stibal, Marek; Jacobsen, Carsten S.; Bælum, Jacob; Taş, Neslihan; Elberling, Bo; Jansson, Janet K.; Semenchuk, Philipp; Priemé, Anders

2015-01-01

The active layer of soil overlaying permafrost in the Arctic is subjected to dramatic annual changes in temperature and soil chemistry, which likely affect bacterial activity and community structure. We studied seasonal variations in the bacterial community of active layer soil from Svalbard (78°N) by co-extracting DNA and RNA from 12 soil cores collected monthly over a year. PCR amplicons of 16S rRNA genes (DNA) and reverse transcribed transcripts (cDNA) were quantified and sequenced to test for the effect of low winter temperature and seasonal variation in concentration of easily degradable organic matter on the bacterial communities. The copy number of 16S rRNA genes and transcripts revealed no distinct seasonal changes indicating potential bacterial activity during winter despite soil temperatures well below −10°C. Multivariate statistical analysis of the bacterial diversity data (DNA and cDNA libraries) revealed a season-based clustering of the samples, and, e.g., the relative abundance of potentially active Cyanobacteria peaked in June and Alphaproteobacteria increased over the summer and then declined from October to November. The structure of the bulk (DNA-based) community was significantly correlated with pH and dissolved organic carbon, while the potentially active (RNA-based) community structure was not significantly correlated with any of the measured soil parameters. A large fraction of the 16S rRNA transcripts was assigned to nitrogen-fixing bacteria (up to 24% in June) and phototrophic organisms (up to 48% in June) illustrating the potential importance of nitrogen fixation in otherwise nitrogen poor Arctic ecosystems and of phototrophic bacterial activity on the soil surface. PMID:25983731

[Quantitative histoenzymatic analysis of the adenohypophysis and adrenal cortex during the early stages of involution].

PubMed

Prochukhanov, R A; Rostovtseva, T I

1977-11-01

A method of quantitative histenzymatic analysis was applied for determination of the involution changes of the neuroendocrine system. The activity of NAD- and NADP-reductases, acid and alkaline phosphatases, glucose-6-phosphoric dehydrogenase, 3-OH-steroid-dehydrogenase, 11-hydroxysteroid dehydrogenases was investigated in the adenohypophysis and in the adrenal cortex of rats aged 4 and 12 months. There were revealed peculiarities attending the structural-metabolic provision of physiological reconstructions of the neuro-endocrine system under conditions of the estral cycle at the early involution stages. An initial reduction of the cell ular-vascular transport with the retention of the functional activity of the intracellular organoids was demonstrated in ageing animals.

SIGN SINGULARITY AND FLARES IN SOLAR ACTIVE REGION NOAA 11158

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sorriso-Valvo, L.; De Vita, G.; Kazachenko, M. D.

Solar Active Region NOAA 11158 has hosted a number of strong flares, including one X2.2 event. The complexity of current density and current helicity are studied through cancellation analysis of their sign-singular measure, which features power-law scaling. Spectral analysis is also performed, revealing the presence of two separate scaling ranges with different spectral index. The time evolution of parameters is discussed. Sudden changes of the cancellation exponents at the time of large flares and the presence of correlation with Extreme-Ultra-Violet and X-ray flux suggest that eruption of large flares can be linked to the small-scale properties of the current structures.

Mining for hemicellulases in the fungus-growing termite Pseudacanthotermes militaris using functional metagenomics.

PubMed

Bastien, Géraldine; Arnal, Grégory; Bozonnet, Sophie; Laguerre, Sandrine; Ferreira, Fernando; Fauré, Régis; Henrissat, Bernard; Lefèvre, Fabrice; Robe, Patrick; Bouchez, Olivier; Noirot, Céline; Dumon, Claire; O'Donohue, Michael

2013-05-14

The metagenomic analysis of gut microbiomes has emerged as a powerful strategy for the identification of biomass-degrading enzymes, which will be no doubt useful for the development of advanced biorefining processes. In the present study, we have performed a functional metagenomic analysis on comb and gut microbiomes associated with the fungus-growing termite, Pseudacanthotermes militaris. Using whole termite abdomens and fungal-comb material respectively, two fosmid-based metagenomic libraries were created and screened for the presence of xylan-degrading enzymes. This revealed 101 positive clones, corresponding to an extremely high global hit rate of 0.49%. Many clones displayed either β-d-xylosidase (EC 3.2.1.37) or α-l-arabinofuranosidase (EC 3.2.1.55) activity, while others displayed the ability to degrade AZCL-xylan or AZCL-β-(1,3)-β-(1,4)-glucan. Using secondary screening it was possible to pinpoint clones of interest that were used to prepare fosmid DNA. Sequencing of fosmid DNA generated 1.46 Mbp of sequence data, and bioinformatics analysis revealed 63 sequences encoding putative carbohydrate-active enzymes, with many of these forming parts of sequence clusters, probably having carbohydrate degradation and metabolic functions. Taxonomic assignment of the different sequences revealed that Firmicutes and Bacteroidetes were predominant phyla in the gut sample, while microbial diversity in the comb sample resembled that of typical soil samples. Cloning and expression in E. coli of six enzyme candidates identified in the libraries provided access to individual enzyme activities, which all proved to be coherent with the primary and secondary functional screens. This study shows that the gut microbiome of P. militaris possesses the potential to degrade biomass components, such as arabinoxylans and arabinans. Moreover, the data presented suggests that prokaryotic microorganisms present in the comb could also play a part in the degradation of biomass within the termite mound, although further investigation will be needed to clarify the complex synergies that might exist between the different microbiomes that constitute the termitosphere of fungus-growing termites. This study exemplifies the power of functional metagenomics for the discovery of biomass-active enzymes and has provided a collection of potentially interesting biocatalysts for further study.

Synthesis, Structural and Antioxidant Studies of Some Novel N-Ethyl Phthalimide Esters

PubMed Central

Chandraju, Siddegowda; Win, Yip-Foo; Tan, Weng Kang; Quah, Ching Kheng; Fun, Hoong-Kun

2015-01-01

A series of N-ethyl phthalimide esters 4(a-n) were synthesized and characterized by spectroscopic studies. Further, the molecular structure of majority of compounds were analysed by single crystal X-ray diffraction studies. The X-ray analysis revealed the importance of substituents on the crystal stability and molecular packing. All the synthesized compounds were tested for in vitro antioxidant activity by DPPH radical scavenging, FRAP and CUPRAC methods. Few of them have shown good antioxidant activity. PMID:25742494

Synthesis, structural and antioxidant studies of some novel N-ethyl phthalimide esters.

PubMed

Chidan Kumar, C S; Loh, Wan-Sin; Chandraju, Siddegowda; Win, Yip-Foo; Tan, Weng Kang; Quah, Ching Kheng; Fun, Hoong-Kun

2015-01-01

A series of N-ethyl phthalimide esters 4(a-n) were synthesized and characterized by spectroscopic studies. Further, the molecular structure of majority of compounds were analysed by single crystal X-ray diffraction studies. The X-ray analysis revealed the importance of substituents on the crystal stability and molecular packing. All the synthesized compounds were tested for in vitro antioxidant activity by DPPH radical scavenging, FRAP and CUPRAC methods. Few of them have shown good antioxidant activity.

Cloning of Trametes versicolar genes induced by nitrogen starvation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Trudel, P.; Courchesne, D.; Roy, C.

1988-06-01

We have screened a genomic library of Trametes versicolar for genes whose expression is associated with nitrogen starvation, which has been shown to induce ligninolytic activity. Using two different approaches based on differential expression, we isolated 29 clones. These were shown by restriction mapping and cross-hybridization to code for 11 distinct differentially expressed genes. Northern analysis of the kinetics of expression of these genes revealed that at least four of them have kinetics of induction that parallel kinetics of induction of ligninolytic activity.

An analysis of flaring and venting activity in the Alberta upstream oil and gas industry.

PubMed

Johnson, Matthew R; Coderre, Adam R

2011-02-01

Alberta, Canada, is an important global producer of petroleum resources. In association with this production, large amounts of gas (1.14 billion m3 in 2008) are flared or vented. Although the amount of flaring and venting has been measurably reduced since 2002, data from 2005 reveal sharp increases in venting, which have important implications in terms of resource conservation and greenhouse gas emissions (which exceeded 8 million tonnes of carbon dioxide equivalent in 2008). With use of extensive monthly production data for 18,203 active batteries spanning the years 2002-2008 obtained in close cooperation with the Alberta Energy Resources Conservation Board, a detailed analysis has been completed to examine activity patterns of flaring and venting and reasons behind these trends in the Alberta upstream oil and gas industry. In any given year, approximately 6000 batteries reported flaring and/or venting, but the distribution of volumes flared and vented at individual sites was highly skewed, such that small numbers of sites handled large fractions of the total gas flaring and venting in the Province. Examination of month-to-month volume variability at individual sites, cast in terms of a nominal turndown ratio that would be required for a compressor to capture that gas and direct it into a pipeline, further revealed that volumes at a majority of sites were reasonably stable and there was no evidence that larger or more stable sites had been preferentially reduced, leaving potential barriers to future mitigation. Through linking of geospatial data with production data coupled with additional statistical analysis, the 31.2% increase in venting volumes since 2005 was revealed to be predominantly associated with increased production of heavier oils and bitumen in the Lloydminster region of the Province. Overall, the data suggest that quite significant reductions in flaring and venting could be realized by seeking mitigation solutions for only the largest batteries in the Province.

YBX1 is a modulator of MIA/CD-RAP-dependent chondrogenesis.

PubMed

Schmid, Rainer; Meyer, Katharina; Spang, Rainer; Schittek, Birgit; Bosserhoff, Anja Katrin

2013-01-01

MIA/CD-RAP is a small, secreted protein involved in cartilage differentiation and melanoma progression. We recently revealed that p54(nrb) acts as a mediator of MIA/CD-RAP action to promote chondrogenesis and the progression of malignant melanoma. As the molecular mechanism of MIA/CD-RAP action in cartilage has not been defined in detail until now, we aimed to understand the regulation of p54(nrb) transcription in chondrogenesis. We concentrated on the previously described MIA/CD-RAP-dependent regulatory region in the p54(nrb) promoter and characterized the transcriptional regulation of p54(nrb) by MIA/CD-RAP in cartilage. A series of truncated p54(nrb) promoter constructs and mutagenesis analysis revealed that the transcription factor YBX1, which has not been investigated in chondrogenesis thus far, is the mediator of MIA/CD-RAP dependent activation of p54(nrb) transcription. A systematic analysis of genes carrying this binding site in their promoter region revealed further potential MIA/CD-RAP-regulated genes that have been implicated in cartilage differentiation. In summary, we described the effects of MIA/CD-RAP on transcriptional regulation in chondrocytes. Understanding the regulation of p54(nrb) via YBX1 contributes to the understanding of chondrogenesis. Uncovering new downstream effectors that function via the activation of YBX1 supports the important role of MIA/CD-RAP in these processes.